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Get The Best Myeloma Care NOW: A Physician’s View

Get The Best Myeloma Care NOW: A Physician’s View from Patient Empowerment Network on Vimeo.

Advocating for yourself is critical when diagnosed with multiple myeloma. Dr. Peter Forsberg details the value of collaborating with your healthcare team on treatment decisions.

Dr. Peter Forsberg is assistant professor of medicine at the University of Colorado School of Medicine and is a specialist in multiple myeloma. More about Dr. Forsberg here.

See More From The Pro-Active Myeloma Patient Toolkit

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Transcript:

Patient education and self-advocacy I think are critical in multiple myeloma. Myeloma is a complicated disease. Getting your head around it can be challenging. Beyond that we have more and more treatments. Treatments are fairly complex. Our goals can be pretty different patient to patient. So really, patient education can be a key to understanding that and removing layers of complexity from something that can be a little challenging to get into.

I think self-advocacy is also really important in that, sometimes you can feel swept up into a wave of what the next treatments are gonna be, what the next steps are. So, making sure you’re taking time to voice your opinions or concerns for yourself, to make sure that you’re not leaving stones unturned in terms of what your best options are, what the best next steps are, what treatments or testing might be available.

I think myeloma, maybe more so than even some other diseases because it’s such a unique type of cancer, one where patients are often dealing with it for many years… Making sure that there’s a good level of education that evolves over time can help make sure that the patients get the best out of their treatments; to make sure that they’re able to have the most fulfilling experience dealing with their cancer and with their cancer team, and making sure that they’re advocating to get all options available to them in the mix potentially.

I think patients are often very thoughtful about knowing that providers are busy and that clinic can be kind of fast-paced, but I want to make sure that they know that the last thing that they’re ever doing is bothering me or other members of my team when they ask questions. I think one of the keys to making sure that everybody is comfortable with the steps we’re taking with their myeloma is to recognize that it’s a team. And the patients and myself and other members of my team, you know I think that the goal is for all of us to be on the same page and to understand what we’re working towards.

So, I think that my philosophy about how best to take care of patients tis to try to make it as collaborative as possible. To make sure people understand what we’re doing and why. And to be all on the same page I think you have to feel comfortable to take a moment to say, “Why are we doing this?” or to voice concerns about what’s going on or what the next steps might be.

How Can Patients Learn About Developing CLL Research?

How Can Patients Learn About Developing CLL Research? from Patient Empowerment Network on Vimeo

Dr. Danielle Brander explains why it’s important for chronic lymphocytic leukemia (CLL) patients to stay up-to-date on developing research and treatment news. Dr. Brander also shares resources for learning more about clinical studies.

Dr. Danielle Brander is Director of the CLL and Lymphoma Clinical Research Program at Duke Cancer Institute. Learn more about Dr. Brander here.

See More From the Path to CLL Empowerment


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Transcript:

Dr. Brander:

I think it’s very important that patients and their caregivers stay informed and advised of opportunities to participate in ongoing research. I think there’s a misconception that with all the favorable progress in treatment options available for CLL, that there’s no longer the need for clinical research participation.

Though, there are a lot of novel options available for CLL, there’s still a lot of ways that we can improve care for patients. That is, there are trials with the next-generation inhibitors or for patients traditionally with harder to treat CLL or may become resistant to the novel agents, there’s a lot of trials looking into how do you combine the novel agents to give patients the best options. And then a lot of the research, too, are not just in the treatments.

But as our science advances into looking at other markers of the CLL cells, or what we call the depth of response, how much CLL you kill with the treatments and how low of a level we can get in terms of detection. This may result in a situation where patients have the opportunity to receive novel treatments, have a really good response, and then potentially stop the treatments and be followed off of therapies, so have the benefit of novel treatment but not with having to go on an ongoing drug forever and ever.

When I talk to a patient about opportunities for clinical trials, I’m really focused on the patient in front of me. That is, I wouldn’t offer or talk about a trial if I didn’t think it potentially could benefit the patient in front of me.

And again, though we’ve had a lot of advances in treatment options, there are certainly a lot of ways that we can engage and hopefully help patients moving forward. There’s been recent studies across all cancers showing that unfortunately a very low percent of patients are offered and enrolled and participating in clinical research studies, and I think it’s really important that patients know there’s a lot of opportunities out there that potentially could benefit them.

The different ways to be advised and informed, again, are some of the resources online educationally for CLL and lymphoma that often post about different sites for clinical trials. There’s a clinical trials.gov web site that all sites in the United States that are enrolling trials with patients have to log clinical trials, and though that has to be updated, it often can be a good beginning site.

But in the end, hopefully the best resource is your treatment team, your oncologist, and your other team that can help point you to what trials might be eligible for you, either at the location where you are or close by.

The last part I’ll point out is though we focus a lot on the treatment clinical trials, in CLL, where patients don’t always need treatment right away or may have treatment and have a response and then have a long period of time afterward, is that many centers are helping to engage patients in research that is not necessarily done during the time of their treatment. Again, to try to understand why some patients have a longer course until they require treatment, or why they might have responded differently, or other ways we can improve their care.

What Is the Impact of Cytogenetics on AML Care?

 

What Is the Impact of Cytogenetics on AML Care? from Patient Empowerment Network on Vimeo.

 Understanding the cytogenetics of your acute myeloid leukemia (AML) can help determine which treatment option might be best for you. Registered nurse Mayra Lee defines this complex term and the role it plays in AML care.

Mayra Lee, RN, is an outpatient clinic nurse at Moffitt Cancer Center. Learn more about Mayra Lee.

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Transcript:

Cytogenetics would be the term that I would say patients are unaware of and don’t understand it quite often. It’s probably the first time you hear it when you come and sit down and we talk about the disease because the first thing you want to know is what is my prognosis and what is the treatment. Well, a lot of that is made through the cytogenetics of the disease.

We use these terms and we don’t often explain what all of that means. And what that means is that the disease itself has chromosomes, has mutations, has genetic information that will help us determine which treatment is a better option for you or is there a genetic mutation that you perhaps have that we now have medications that are used to treat that genetic mutation as a said just a few seconds ago. Like for the three, if you have that mutation, we now have medication to treat that where we didn’t have that five years ago or even four years ago.

 So, that terminology of cytogenetic and biomarkers are very new. They’re not something that the general public knows or understands very well.

But when you come to academic centers like where I’m at right now that is all we’re going to talk to you about because we want to do personalized medicine. And personalized medicine means what is it that your disease looks like because your disease does not look like the other AML patients. Your disease is your disease and it looks different and it’s going to behave differently. And so, we want to know about those mutations. So, so much of your treatment, so much of the prognosis is so closely linked to that that I think it’s an important thing to know. It’s important to understand it. It’s important to ask. It’s important to pause your doctor and your nurses and say, “I don’t understand what you mean by that. What does that word mean? Can you explain that to me?”

What Should CLL Patients Know About Their Blood Work?

Ask the CLL Expert

Ask the Expert: What Should CLL Patients Know About Their Blood Work? from Patient Empowerment Network on Vimeo.

CLL experts Dr. Susan Leclair and Dr. Justin Taylor discuss how to understand testing with CLL, how CLL patients can advocate for the correct testing, making the most of doctors’ appointments, and more.

Downloadable Resource Guide


Transcript:

Andrew Schorr:

And hello from Southern California. I’m Andrew Schorr. Welcome to this Patient Empowerment Network program produced by Patient Power. We’re so delighted you are here. I’ve been living with CLL since 1996. And so, testing was not as sophisticated then, and it’s come a long way and there are a lot more choices now. So, in this program, we will be discussing how do you know when you need treatment? What tests are important when you’re in a sort of watch-and-wait period? If you start treatment, how do you know if it’s working? How it’s monitored? If you’re in remission? How do you know how deep that remission is? Should you need treatment again, are there other tests that need to be repeated, or new tests to be done? Lots to talk about. I want to thank the Patient Empowerment Network for putting this all together, and for their financial supporters who have no editorial control, that is AbbVie and Pharmacyclics. So, thanks to them for supporting patient education. Okay. If you have a question, send it to cll@patientpower.info. Many people have, so we got tons of questions, and we’ll get through as many as we can in this Ask the Expert program, helping all of us with CLL understand our blood work and what’s needed and when. And we have some great guests with us. First of all, I wanna go to my dear friend who I’ve know most of these 20-plus years as I’ve been living with CLL, Dr. Susan Leclair, laboratory science guru. She joins us from Dartmouth, Massachusetts. Hi, Susan.

Dr. Leclair:

Hi.

Andrew Schorr:

Welcome back to our program.

Dr. Leclair:

And I think we were both very young when we first met.

Andrew Schorr:

Well, you didn’t have grey hair. But I cannot say that I had a full head of hair, but here we go. And I didn’t lose it because of chemo. It was gone, hereditary. Okay. And now let’s scoot down to New York City to one of our top cancer centers in the world, Memorial SloanKettering, where we’re going straight to the lab. And that is Dr. Justin Taylor, laboratory researcher, and also CLL clinician. Justin Taylor, thanks for being with us.

Dr. Taylor:

Hi, Andrew. Thanks for having me. Happy to be here.

Andrew Schorr:

We’ve been wanting to get you with us for a while. And he, folks, is where action happens. They start with mice, and then they start working on what does it mean to all of us with our blood? And, of course, human clinical trials, and Memorial Sloan-Kettering has helped lead the way. Okay. Susan, are you ready to go?

Dr. Leclair:

Sure.

Andrew Schorr:

Okay. So, people worry, what about their tests? And one thing I wanna get off our plate right away, and I’ll just say it for me. So, I get immunoglobulin infusions once a month to boost my immunoglobulins. And you can help us understand what that is. And I get a blood test at the same time. And I worry if the platelets go up a little, or the platelets go down a little, or and then there’re all these MCVs and blah, blah, blah. I don’t understand what they mean. And I worry sometimes if there’s a little blip. But we really worry about—we’re not even worried. We watch the trend, right?

Dr. Leclair:

Right. I would not panic unless you see two consecutive numbers going in the same direction. Now there are a lot of caveats to that, but we don’t have five days on the program. So, basically, statistics don’t work, unless you’ve got at least three values. So, if you started at a value of 1.0, and the next time you got it, it was 1.5, and the next time you got that same test it was, I don’t know, 0.62, they’re not in the same direction. There’s no big change. You’re kinda okay.

You begin to worry only if it goes from a 1.0 to a 2.5 to a 5.0. Now you’re beginning to get a sense that things might be moving in a specific direction. So, you wanna wait. I know it’s not watch-and-wait; I know it’s watch-and-worry. But you have to wait for at least the third one of the values. It’s part of the reason that your physician will use that horrible word, “Fine,” when they look at things, and they say, “Oh, no, this looks fine.” It’s because they’re not seeing that trend going in one direction or another.

Now some tests, you want the trends to be higher; some you want lower. But think about you need three values going in the same direction in a row before something can be considered worthy of, well, worry, or at least worthy of a question.

Andrew Schorr:

Okay. Thank you for that. Justin, I wanna ask you about something we talk about a lot now in CLL, and as you get to the different chromosomal deletions, I guess you call it. So, we’ve known for a long time that one that led to more aggressive CLL was the 17p deletion.

Dr. Taylor:

Yes.

Andrew Schorr:

And now we have medicines that kind of work on 17p, which is cool. So, we got a question from Robert Schneider who said on the CLL patient with 17p, been treated in his case with Venclexta or venetoclax for two years, and had reached MRD, minimal residual disease negative in my bone marrow and blood, what are the pros and cons of stopping treatment if I’ve had this 17p? So, where are we now measuring 17p? And help us understand this MRD level.

Dr. Taylor:

Okay. Yeah. Lots of great points there. I’m glad you brought up the 17p. That is historically a more bad prognostic marker, although as you’ve brought up, we now have drugs that can work for patients with 17p deletions. So, we’re very excited in the clinic to have Ibrutinib and Venclexta, or venetoclax—I’ll use the generic names—as options for our patients with 17p deletions, or other abnormalities that include genes on 17p such as the p53 gene.

And so, those are effective. And we’ve seen some patients that have been lucky, as David, to get into a minimally residual disease, or measurably residual disease negative state from these treatments. But I’d say it’s still the level of our knowledge, at this time, does not allow us to know whether it’s completely safe to stop. And that’s something that’s currently being tested in clinical trials, both in the US, as well as abroad.

And so, we have a trial here at Memorial Sloan-Kettering testing patients who have been on Venclexta and get into this MRD-negative state. If they’re able to stop the drug and it’s basically randomizing—or not randomizing people, they’ll be allowed to decide whether they wanna stop or not.

And then following them to compare the patients that stop versus the patients that didn’t stop to see what the difference in terms of relapse rates are, overall survival, whether it is gonna change the outcome of the disease whether you stop or continue on the drug. So, that’s a great question, and it’s currently one that we’re trying to answer as fast as possible.

Andrew Schorr:

Okay. And, Susan, just so we understand this MRD, these are super-sophisticated tests, right, now looking for cancer cells at like I almost think, maybe not the nano level, but, right? And we haven’t had these for a long time.

Dr. Leclair:

Oh, no, they’re relatively new. For those of us who do have different colored hair than what they started out with, once upon a time, it was one CLL, and we had no treatment for it. And now we have multiple versions of CLLs. And we have, oh, maybe, I don’t know, 10 possible different fairly well-known, fairly well-described genetic anomalies. You’ve got different drugs that go along with it.

So, in each one of those, complexity adds confusion at the same time. So, some of our tests are—oh, no, I take that back. All of our tests have limits. I test for something, and my limit is one in a billion. Well, supposing you have one in two billion? I’m going to come up with a negative, not because there’s nothing in there, but that it is there at such a low number, I can’t pick it up.

So, there are times when you have these results, and minimum residual disease is a great phrase for it. All I can tell you is to the limit of my testing, to the limit of every scientific test we have out there, I can’t find a malignant cell of your CLL in there. Does that mean that it’s absolutely not present?

Andrew Schorr:

Right. But we can measure it better than ever before. And it gives us some confidence. And I think patients want to know. But so, that goes to Justin. Justin, you’re at one of the largest cancer centers. There you are in the lab, and you do all sorts of sophisticated testing. But many of our viewers are around the world and they’re not necessarily being treated at a big academic medical center.

So, the question is, what tests are necessary? So, maybe you could help us understand. If you are out there in the hinterland, and you needed to help yourself as the physician, and the patient just kind of understand what’s going on, what’s the basics? So, first, let’s start at diagnosis. What’s the basics to know what’s going on? Do you have to have a bone marrow biopsy? Do you do CBCs? Do you have to do what we call FISH testing mutational status? What’s like the basic?

Dr. Taylor:

Yeah. Thanks. And we definitely can do, as Susan was saying, many, many tests with different sensitivities and specificities, but kind of the gold standard of proving whether adding these tests makes the difference is to do a clinical trial or a prospective trial, I guess, where you measure these things before patients get treatment, and then see which of them makes a difference in the outcome.

And when you add them all into a kind of analysis that includes all of these tests, which ones are important of themselves because some tests are markers, basically, of something else that you can measure. So, that being said, there have been many studies like this to try to see whether we can add in any of these new tests that have been developed in the decade to the kind of gold standard. And many times all of the new tests that we add aren’t able to distinguish that much more than what the basic tests show, so I…

Andrew Schorr:

…okay. So, literally, let’s just tick off some. Bone marrow biopsy; critical to do?

Dr. Taylor:

That’s very controversial. We still do that. I don’t think that it’s critical in making the diagnosis. That could be made from the peripheral blood flow cytometry, which tells you the markers on the surface of the cell, that they’re different than normal B cells. We still do the bone marrow biopsy to get a sense of the stage of the disease, how much CLL there is. But it’s not absolutely required for the diagnosis.

Andrew Schorr:

Oh, okay. And what about so-called FISH testing; is that important?

Dr. Taylor:

I think it’s important, based on what we talked about with the 17p deletion. It can detect that. That’s a big change on the DNA, on the chromosomes, that can be detected by FISH. And, yeah, many of the tests I was referring to before are looking at specific genes. I don’t think that those are necessary. They definitely can give some insight to the treating physician, but.

Andrew Schorr:

Okay. And then the last one is that I always get this backwards—is it IgVH, IvGH—but the mutational status, why is that important?

Dr. Taylor:

Yes, the IgHV mutational status, if I got it right, is important because there’s—basically falls into two camps. You can have unmutated and you can have mutated, and you would think that the mutated would the worse, but it’s actually the unmutated that has the worse outcomes.

And that’s important, because it’s been shown that this unmutated set of IgHV-unmutated CLL may not be the type of patient that you want to give chemotherapy to. They may not respond as well to chemotherapy. That may be something you want to go straight to one of the new agents.

And for the mutated patients, which have a little bit better prognosis, new agents are definitely on the table for them also, but there’s a subset of those patients who, with chemotherapy, a study done at MD Anderson that followed these patients 20 or more years after chemotherapy, a subset of those with IgHV-mutated CLL did not require further treatment. Essentially, we didn’t say that they were cured, but they were as if they were cured. They only got one treatment with chemotherapy and never required anything again.

Andrew Schorr:

Right. Well, okay. Let me raise my hand. I was in the Phase II trial for chemo, fludarabine (Fludara), cyclophosphamide (Cytoxan) and then rituximab (Rituxan) added in 2000, and I had no other treatment after six months of therapy for 17 years.

Now, I had an MRD test along the way, and dear Dr. Wierda at MD Anderson said, “You know,” with the testing they had then and this is several years ago, “You’re not MRD-negative. You’re probably gonna need treatment again. I feel confident you will.” And so, I knew there’d be another shoe drop. But with the chemo, I did get a long remission. Susan, one of the questions we’ve had is, and you’ve heard this before, people get different lab values from different labs.

Dr. Leclair:

Yes.

Andrew Schorr:

Maybe they had it here. So, you’re like in the international organizations. Shouldn’t there be like one standard; if my hematocrit is this, that’s where it is for everybody? I mean, why does it vary?

Dr. Leclair:

Because you do. One of things that is critical here is that you, the patient, have different levels of hydration from the morning when you get up. This makes absolute sense when you think about it. When you roll out of bed in the morning, you’re not really as well hydrated as you might be at 4:00 in the afternoon, or that you’re not as well hydrated after you’ve run for two hours than you were before it.

Since most of the initial blood work that you use, both in diagnosis and in monitoring, is based on volume, if you got diagnosed with a CBC that was drawn at 3:00 in the afternoon, for the name of consistency, could you keep having your blood drawn at 3:00 in the afternoon? Because that will provide us probably a more constant basis of you are hydrated at this level all of the time.

Andrew Schorr:

Right. But you know what—yeah, but I’m not asking just that question. If I go to the same lab and test at the same time and drink water before, but so, we get lab test results, and in the case in San Diego, it has H’s and L’s, highs, lows, out of the normal range, and I got a bunch of them, okay? But what I wanna know is, is that standard of what’s within the normal range the same at every lab? Or if it isn’t, how come?

Dr. Leclair:

Well, in the case of hemoglobin, for example, if you live in Telluride or Vail or Aspen, you’re at a higher level. There’s a lower amount of oxygen in the atmosphere, so you need more hemoglobin to grab the oxygen from your inspired breath and bring it to the tissues. So, pretty much everybody who lives above Mile High Stadium, so to speak, it’s not that anymore, but everyone will remember it, is probably gonna have a higher hemoglobin than somebody who’s at a lower one.

If I’m in the lab and I’m developing a set of reference ranges for the physicians in that area, then if you come bouncing into Vail and have a CBC, you’re still at your California seaside hemoglobin level. To somebody who’s expecting people to have a higher one, you will look as if you have a lower hemoglobin.

Andrew Schorr:

Right. And I’m going to Colorado in a week or so, so, yeah. Okay. I get it. That was a question we had from several people. Now, Justin, I got a question from you. A lot of the people here, a percentage, have been diagnosed with SLL, not CLL, but we understand they’re basically treated the same. So, help us understand the difference. But what they want to know is should their testing be different?

Dr. Taylor:

Yeah, that’s a great question. We do think of them as the same disease. It’s just the manifestation. In CLL, the abnormal B cells are mostly circulating in the blood, leading to abnormal blood tests with high lymphocyte count.

Whereas in SLL, or small lymphocytic lymphoma, a name that was given because primarily, the abnormal lymphocytes are in the lymph nodes and they don’t circulate in the blood, so patients with SLL would be detected because they have abnormal lymph node swelling.

They might go to a physician who primarily treats lymphoma, which is another related disorder that presents with abnormally enlarged lymph nodes. And so, they oftentimes are monitored different, treated differently, because the cells are not circulating in the blood, so they can’t be detected as easily through a blood test.

So, in my practice, I use the physical exam and monitor wherever the lymph nodes are through examining them, just physical examination. And you can also do a CAT scan, or a CT scan it might be called as well, to measure throughout the body the places you can’t examine within the thorax and abdomen if there are lymph nodes there also.

Andrew Schorr:

Okay. So, the cells are not floating around, so it’s a little different as far as monitoring goes. Okay. So, let’s get to monitoring. Justin, I’ll ask you this, too. So, people wonder, okay, if I’m in remission, how often do I need to be monitored? So, you’re doing the physical exam. My doctor, Dr. Kipps, feels for lymph nodes. He digs under my armpits. He does a lot of stuff.

And that part’s not fun. But and I get these regular blood tests monthly, which are just zapped to them when I get my immunoglobulin, so they’re keeping a watch on me. And I should mention that I have another condition, too, myelofibrosis. So, I got two doctors watching me pretty carefully. But, basically, I don’t see them very often. So, related to testing, is that really an individual thing with your physician as far as just like CBCs, Justin?

Dr. Taylor:

Yeah. To me it’s dependent on each patient, and, as Susan mentioned, the trend of the blood counts, and what treatment you got, how long ago that was. In a general set of rules, the sooner it is after treatment, you might be monitoring it more closely. And then as time progresses, everything’s been looking okay, the time can be spread out, again, based on the individual patient. If there’s continuing, ongoing reason to watch some specific lab test then, as you mentioned, it might be done every so often.

I would say unless there’s something particularly that you’re keeping an eye on, such as you immunoglobulins, you probably don’t need it once a month; every three months is generally acceptable, if everything looks normal, there’s nothing. But in your case, you’re getting these IVIg infusions, and so, they’re testing the levels to make sure you need them every month. And so, it comes down to each individual patient.

Andrew Schorr:

Susan, so, we mentioned this a couple of times, IVIg. And some of our patients who are on this program get it, too. So, what is immunoglobulin, or what are Igs? What is this stuff?

Dr. Leclair:

Immunoglobulins are essentially proteins. They can be transport proteins. You eat a steak, your body absorbs the iron, and it needs to get put on a transporter, so that it can be moved around. So, there’s transport proteins. There are modifying proteins that control how fast or how slow something’s gonna happen.

But the ones you are interested are the immunoglobulins that are antibodies. Now we all know about antibodies because there’s certainly been enough argument across this country in the last few years about antibodies in terms of getting immunizations for children against measles and mumps and other childhood disorders, whether or not it’s Zika, and all the rest.

You have in you, over time, built up a body of antibodies, a collection, an encyclopedia of antibodies that remember that you had that disease 22 years ago. And while you’re not actually making a whole lot of those antibodies, you’re making enough of those antibodies to make sure you’re never gonna get it again.

What happens with CLL folks is that they don’t make either functional antibodies, or they don’t make enough, which means that you at your age might have had an immunization for mumps a long time ago. My guess is you don’t want to have mumps right now. So, we should give you some pre-informed, pre-manufactured antibodies against mumps that will help whatever cells that are in your body that are trying to make mumps antibody to give you enough mumps antibodies so that you never get mumps again.

So, this a procedure that is giving you this infusion of antibodies, is to keep your system at a place where it won’t get sick when you’re in a subway and someone sneezes, when you’re in a restaurant and someone coughs at you, when you find yourself somewhere with a friend who says, “Gee, I hope you don’t mind, but I’m still getting over X.” So, it’s protective for you.

Andrew Schorr:

Okay. And Dr. Kipps here in San Diego says, “Andrew, if you want to travel,” and that’s true, and I like to travel, and we’ve seen many of our CLL friends when we do, he said, “You gotta have the IVIg infusions.”

Andrew Schorr:

Justin, just so we understand, what about—she mentioned immunizations. First of all, where does immunoglobulin come from? My understanding is it’s made from somebody else’s blood. I’m getting like a blood product, hopefully, squeaky clean in that, and I’m getting some immune benefit from that. Is that the idea?

Dr. Taylor:

Yeah, that’s correct. So, the antibodies come from B cells, and that’s why CLL is a disease of the B cells. And so, that’s why they’re, as Susan mentioned, they’re not forming the proper antibodies. So, we can get these healthy antibodies from donors, and it’s usually a pool of those antibodies to get enough to give you that boost.

And I just wanted to mention that not every patient with CLL needs these. You can measure the immunoglobulin levels in the body, and if they’re normal, you may not need the extra boost, especially if you’re early CLL and watching and waiting. And, again, and if patients are getting recurrent infections, that’s another reason that they might need transfusion.

Andrew Schorr:

Right. Yeah, and I’ll mention, to be clear in my case. So, I went 17-year remission, folks. I did get some sinus infections. Usually, if I got a cold, I got sinus infections, took antibiotics, quicker than people who don’t have CLL, of course, and it knocked it out, okay.

What we noticed is, after I had retreatment for CLL with a monoclonal antibody, obinutuzumab or Gazyva, with steroids in my case, about almost two years ago I was getting more often infections. The CLL was controlled, but, like Susan just said, my immune system was inept and it needed some help. And so, Dr. Kipps decided I needed IVIg. But that’s a personal thing with you and your doctor. You may be monitoring how frequently, just what Justin just said, how often you’re getting infections, because it’s certainly not for everybody.

Okay. So, let’s talk. I wanna understand something, Justin. CLL can change over time. So, we mentioned the 17p deletion, or people hear this other alphabet soup, 13q, and all these different things, or trisomy, and all these things. So, the way you start out, is that the way you may be years down the road? And if not, how come?

Dr. Taylor:

Yeah. For some reason, CLL can change. A term you might read about is it’s called clonal evolution. It sounds like “Star Wars” with the clones, but you can basically have the CLL that you started with, it can acquire other mutations, or other abnormalities that you’ve listed there over time, so, even untreated CLL, does change over time. We don’t really understand fully why that is. We know, in general, cancers do that, so CLL seems to be at the faster rate of that ability to change the genetics.

And so, I think the CLL you end up with might not be the same as you started with. And so, this comes to another question that was asked of when to do this testing for 17p IgHV. You often hear the argument that you don’t need those until you’re gonna start treatment because if you get them at diagnosis, and then you’re gonna not start treatment right away, they may change over time, and you wanna reevaluate those at the time of treatment.

So, that is why some patients might not have all the testing done at the time of diagnosis. Not every doctor feels that way, so some patients do get all the tests run at diagnosis, and then again when it’s time for treatment based on the progression of the disease and symptoms. Then often we repeat those just because there’s the possibility that within that time frame, whether it’s a year or several years, that these markers can change.

Andrew Schorr:

Susan, you and I have been around this a long time, and you remember one of the really wonderful patient advocates years ago, Granny Barb Lackritz. Barbara Lackritz. We called her Granny Barb. And one of the words she told us Esther and me, years ago when I was diagnosed, was, “Chill out.”

So, have this array of tests now. And there will be some of our viewers who say, “Okay, I want this test, and I want this test, and I want this test, and I want this test.” And, “Oh, my God, this has moved a little.” And, “Do I need to be retested?” What you tell people to kind of take a deep breath, even though you have this array of testing now?

Dr. Leclair:

I tell them to take a deep breath and to slow down. This is not a disease that is going to “harm you.” That may be in quotations. This is not a disease that will harm you today or tomorrow or even in a year. This is a disease that will allow you to think it through. Well, not necessarily slowly, but deliberately. What you wanna do on these tests is not say, “I want every single one of them.” Because then you’ll get a lot of information you can’t interpret. What you want is, “Let’s do one test at a time.” The results of that test will lead you to the next test.

For example, the CBC gives you a very high white count, and it looks like it’s all lymphocytes. Okay, what do you do next? Well, the next logical question is: Who are these lymphocytes? What are they doing? So, that’s when you do the flow cytometry, and you find the answer of who are they at a gross level, at a fairly simple level. Oh, they’re B cells, or maybe they’re T cells. And in that answer then provides you with the next thing you want to do.

So, instead of ordering them all like eating and taking every single bite out of a huge buffet, you might wanna just wait and follow the detective story as it goes along. And what that will allow you to do is, well, these were my answers in September. Well, these are my answers plus a new one in November. Oh, well, these are my answers in September and November, and now in February. And so, you begin to develop a story. You begin to know your cells. Your physician begins to know your cells.

You can say things like, “Oh, well, in January, I had a cold.” All right. Let’s about then how that cold might have affected the results in January. You already know what the results were in September and November. Let’s look at this in context. You have the time. Use it.

Andrew Schorr:

Right. Now, Justin, we’re talking so much about testing, but you referred to physical exam. So, I think we have to be fair and say you guys look at the complete picture. Like, for instance, is my spleen enlarged? Do I have night sweats?

Do I have new lymph nodes? How big are they? Where are they? Right? Am I getting a lot of infections? Right? So, you gotta look at the whole picture, right? It’s not just the numbers. Correct?

Dr. Leclair:

Absolutely.

Dr. Taylor:

That’s right. Absolutely. Yeah, it’s personalized medicine before that term came to mean doing genomics. It’s every person is different; every situation is different. As Susan mentioned, situational things can happen with infections that change the numbers, and it’s important that – We’re not gonna be able to guess that, so discussing with the patient, hearing the history, taking the time to do the exam, and then, again, putting that into the context and the historical context with that patient.

So, that’s why the patient-doctor relationship is very important. Of course, it’s always recommended, if you want a second opinion, to hear from another doctor or someone that specifically does CLL. But just having your physician that’s known you for a long time is very valuable, as well.

Andrew Schorr:

Let me put in a plug for second opinions for a second. So, Justin’s at one of our premier cancer centers, Memorial Sloan-Kettering. There’re a few of them in New York, where he is. There may be one this way down the interstate from you in New York, or in London, wherever you may be.

And I would say, with a long-term illness, it gave me confidence to check in with an academic medical center. And I actually had teamwork, when I was in a clinical trial, between a local cancer center and a university cancer center.

And I got those doctors talking. That gave me confidence. And when I needed treatment, actually, and ultimately in a trial, they worked together.

So, one of the questions came in and said, “Well, when should I check in with a CLL subspecialist like Dr. Taylor is, even in the lab?” Well, along the way. But as Susan said, “The house is not burning down today.” Okay?

Now, Justin, you’re in the lab there. I have a question for you. So, I have three kids. And one of them, and some people know, are Ruthie, are the producer of this program. And so, we wonder, when you talk about genomics, is there some test we should do to see if my children are at risk for CLL? And should we do that routinely, like you might do in some other more hereditary conditions, when we really don’t know, is there a real hereditary connection in CLL?

Dr. Taylor:

Yeah. We talk about the genetic tests, or the genomic mutations, and that always invokes something hereditary in the genes. But when we actually do these tests here at Sloan-Kettering and other places, we will take the CLL cells, take the DNA from those, and we also get a sample of normal tissue. So, often it’s a swab of the side of the cheek, a swish of saliva, sometimes fingernail DNA, something that we can get that we don’t think has any CLL in it.

And then we sequence them both, and we’re comparing the CLL cells to the normal cells to try to detect the mutations that occurred in the CLL that make them different than the normal cells. So, all of these mutations that we’re talking about are something that happened in the CLL cells sometime during your life. And we’re finding out now that these could have been there, these mutations could have been there for years before they finally manifest this CLL. But they’re not something you were born with. They’re not in the cells of your body or the cells that are passed down to your children. There are very rare cases of heredity CLL, but my understanding is they’re exceedingly rare. I haven’t come across them, but they’re reported in the literature. So, if there’s a very, very strong family history of cancer between generations, a bunch of siblings have a cancer, then that might be a time to consider hereditary genetic testing. Otherwise, CLL is typically thought to arise in these cells along your lifespan. You’re not born with them. They’re mutations that are occurring as you age.

Andrew Schorr:

Okay. So, I’m not recommending my kids get some tests. And also, I’d say, and Susan knows this so well, and Justin, as you’ve gone through your training and graduated to be in the lab and seeing patients, everything’s changed. Everything has changed during my time. And so, if God forbid, one of my family members developed CLL years down the road, it’s gonna be different from what it is now. It’s gonna be different.

So, Susan, just so we understand, go back to something that we talked about, about clonal evolution, okay? And the CLL kinda changing, taking the winding road. Is it the idea that the cancer cell is kind of trying to figure out a way around the medicines, and just proliferate? It’s like sneaky?

Dr. Leclair:

Oh, they’re definitely sneaky. That’s absolutely correct. There are a number of situations that are involved in here.

We don’t really know which one goes with which disease, or if maybe more than one does. But, yes, I suppose, philosophically, you can think of these cells as wanting to live. And they’re gonna do whatever is necessary for them to live. So, you hit them with a medication that is rituximab, probably one of the better known ones. Rituximab hits a particular compound on the cell. And the loss of it, a lot of times, will cause the cell to be damaged and die.

Well, on the cell, and I’m a little on the smart side, I’m just not gonna make that marker on your cell. Or I’m going to put a hinge on it so that it breaks off, so that there’s minimal damage to me. And so, those kinds of things can and do happen to those cells. There is also the issue that, whether we like it or not, every day we go out and interact with something that’s gonna challenge ourselves or our genes in some way.

Three weeks ago, I went to the dermatologist with my husband, because he’s the one who has problems. We walked into this guy’s office and he said, “I’m taking you first. You have skin cancer.” “Excuse me?” That was a surprise to me. Well, how did that happen? It couldn’t have been because I’ve spent a lot of time outside without a hat on or anything like that, but I am not 22 years old. This took a long time for this to happen to me.

So, that’s a sense of a clonal evolution that occurs with repeated incidents of stress. And we all have that, every single day. Sometimes the only thing that happens is nothing. Sometimes you have to get your nose skinned to get stuff off.

And that’s what happens with these cells, as well. They will adapt because they want to live. We don’t, but they do. It is a matter—a contest to see who wins.

Andrew Schorr:

So, Justin, there you are in the lab. And as we come to the end of our program, I guess we wanna make clear, we talked about the whole picture, not just lab tests. But you’re looking at what could be tomorrow, okay. So, it sounds like there’s a pretty good pipeline of treatments of CLL should you have this clonal evolution, whether it’s 17p or something else, where you are gonna have something, please God, to bop it on its head again. How do you feel about it?

Dr. Taylor:

Yeah, we have good treatments now. We mentioned a few of them. I’ll just list some again. Ibrutinib (Imbruvica), venetoclax, idelalisib (Zydelig), obinutuzumab was mentioned, rituximab was mentioned, chemotherapy was mentioned. And so, we have a lot of tools and armamentarium in our pocket. But despite that, none of these are home runs, as it was put recently. So, we’re still trying to come up with other things and figuring out how to sequence them.

So, if you start off on Ibrutinib and then you can go to venetoclax, is that better? Or should we put the two together up front? And that was recently tested. We’re comparing these things and trying to figure out what’s the best way to give them in combination or sequentially to try to prevent this clonal evolution. And in the meantime, we’re coming up with more things to use in the future should these combinations not work.

Andrew Schorr:

Right. And you are. And I just wanna echo something that really the father of CLL study and treatment, Dr. Kanti Rai, talked to us about years ago, as we saw more of these tools you have come together, and you continue as, he said, to try to figure out how to arrange them.

It’s like arranging furniture in the room. There’s more furniture than ever before and you, Dr. Taylor, and your peers start to figure out how to arrange it, and people in laboratory science, Susan’s students, try to give you data to go along with the physical exam to get the whole picture of where that individual patient is. Did I get it right, Justin?

Dr. Taylor:

Perfect.

Andrew Schorr:

Okay. Susan, thank you so much for your devotion. What I get from you, always, is like what Granny Barb says, “Chill out.” You said, “Take a deep breath.” We’re on a long-term journey with CLL. And thank God we have a greater array of treatments. Are you hopeful for all of us, Susan?

Dr. Leclair:

Oh, I’m very hopeful. I think there will be a time when we will see the last person with CLL, just like we will see the last person with a lot of other ones. Look at yourself, Andrew, it’s the perfect example. Seventeen years ago you said, “Oh, God, what am I gonna do? I have to have therapy.” And you had the only therapy we had, and you got 17 years. And now when this happened, you said, “What am I gonna do?” And I said, “Have another 17 years.”

Andrew Schorr:

Right. Right, right. She did. And Esther and I just got back from Sweden, and we had a great time.

Dr. Leclair:

Oh, I’m sure.

Andrew Schorr:

I am so grateful to the medical community, the pharmaceutical community, the healthcare providers. I wanna thank the Patient Empowerment Network for putting this all together. I wanna thank AbbVie and Pharmacyclics for funding it. They had no control. Justin said what he was gonna say. I said what I was gonna say. Susan said what she was gonna say. Justin Taylor, thank you for being with us from New York in your lab. Go get ‘em, Justin.

Dr. Taylor:

Thank you.

Andrew Schorr:

Cure CLL, okay? Susan, thank you so much. You’re retired, but not really. You’re never retired for us, okay.

Dr. Leclair:

You told me I couldn’t.

Andrew Schorr:

No, you’re not allowed to retire. Okay. In Southern California, for Patient Power, but for the Patient Empowerment Network, I’m Andrew Schorr. Remember, knowledge can be the best medicine of all.


Please remember the opinions expressed on Patient Empowerment Network are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Facing Acute Myeloid Leukemia: Notes from a Survivor

In the spring of 2016, I was looking forward to a final year of teaching sociology before a retirement promising new adventures.  I felt great and had no reason to think I had any health problems.  When my doctor suggested some routine blood work, I readily complied.  When the results showed abnormally low white blood cell counts and he recommended a hematologist, I readily complied. When the hematologist ordered a bone marrow biopsy, I still readily complied.  When the results came in, my life changed forever.

The biopsy revealed that I had acute myeloid leukemia. Since this disease can kill within months, they recommended immediate treatment. The next day I checked into a hospital and started chemotherapy.  I received the standard treatment for this disease for the preceding 40 years: a “7 + 3” cocktail of cytarabine and idarubicin.  I spent five and a half weeks in the hospital dealing with various infections brought on by immunosuppression and patiently waiting for my blood counts to recover. As they did, I received the best possible news. The chemotherapy had achieved a temporary remission that bought me time to explore my options for longer term treatment.

As I awaited the molecular and cytogenic data on my cancer, I was told to expect two possibilities.  If there was a relatively low risk of relapse, I might get by with additional chemotherapy. If there was a high risk of relapse, a stem cell transplant was in order. When the results placed me in an intermediate risk category, I had a tough choice to make. After researching my options, getting second opinions, gathering advice, and reading my doctor’s cues, I settled on the transplant.  My logic was that if I opted for more chemo and it didn’t work out, I would deeply regret not having the transplant.  If I had the transplant and it didn’t work out, at least I would feel as if I gave it my best shot and it just wasn’t meant to be. Despite the 15-20% mortality rate from the transplant itself, I was at peace with my decision to proceed.

My benefactors were two anonymous sets of parents who had donated their newborn infants’ umbilical cords to a transplant bank.  Once we found two good matches, the cords were shipped to my transplant hospital, the cord blood was extracted, and it was transfused into my bloodstream. These stem cells just “knew” where to go to engraft in my bone marrow and begin producing a healthy new immune system.  For the second time, I received the best possible news. Three weeks after transplant, one of my donor’s cells were 99% engrafted. With that result, I returned home for a prolonged recovery.

For the next few weeks, I faced daily clinic visits, blood tests, transfusions of platelets and red blood cells, growth factor injections, and lingering effects of my conditioning chemotherapy and radiation as well as the engraftment process itself. As the weeks turned into months, my recovery proceeded apace.  It eventually became clear that I could claim the best possible news for the third time, as my new cells and old body got along with each other and there was no evidence of graft-vs.-host disease.  Looking back over the entire process, my oncologist summarized it by saying “this is as good as it gets.”

Many people wanted to give me credit for surviving this disease. While it is tempting to claim such credit, I remain agnostic about whether anything I did had a material effect on my positive outcome. I think my survival was largely a matter of luck, chance, and random variation across AML patients. Nonetheless, there were several practices I engaged in throughout my treatment that deserve mention. At the very least, they brought me peace during a difficult time. And at the most, they may indeed have contributed to a positive outcome for which I am eternally grateful.

The first set of practices that sustained me was mindfulness, meditation and yoga.  To the greatest extent possible, these practices helped me let go of ruminations about the past or fears about the future and focus on the present moment.  Focusing on my breathing kept me centered as – like my breaths – each moment flowed into the next.  Maintaining a non-judgmental awareness and acceptance of each passing moment kept my psyche on an even keel.

Rather than extended periods of formal meditation, I simply sought a mindful awareness of each moment, hour, day and week.  I also went through a daily yoga routine even while receiving chemotherapy. Doing so helped me retain my identity as I weathered the toxic treatment and its inevitable side-effects.  In the evenings, I used a technique called a body scan to relax and prepare me for a peaceful sleep. The cumulative effect of these practices was a calm acceptance of circumstances I could not change alongside a serene hope that all would work out for the best.

A second practice involved being a proactive patient.  Perhaps it was my training as a social scientist that allowed me to bring an analytical curiosity to my disease and the treatments my doctors were deploying. I asked lots of questions during their all too brief visits, and they patiently responded to all my queries.

On several occasions, my proactive stance made a positive contribution to my treatment.  When I developed a nasty, full body rash, it took a collaborative conversation between me, my oncologist, and infectious disease doctors to isolate the one drug among so many that was the culprit. I identified it, they switched it out, and the rash abated. On another occasion, I was able to identify two drugs that were causing an unpleasant interaction effect.  I suggested changing the dosing schedule, they concurred, and the problem resolved.  The sense of efficacy I received from this proactive stance also helped me retain a positive mood and hopeful stance during my prolonged treatment.

A third practice involved maintaining a regimen of physical activity.  During my first, five-week hospital stay, I felt compelled to move and get out of my room for both physical and social reasons.  I developed a routine of walking the halls three times a day, trailing my IV pole behind me.  They tell me I was walking roughly 5 miles a day, and every excursion felt like it was keeping my disease at bay and connecting me with all the nurses and staff members I would encounter as I made my rounds.

When I moved to my transplant hospital, I was confined to my room but requested a treadmill that met the physical need for activity even as I sacrificed the social benefits of roaming the halls.  But throughout both hospital stays and later at home, I maintained stretching activities, exercise workouts, physical therapy routines, and yoga to keep my body as active and engaged as my circumstances would allow. These activities also gave me a welcome sense of efficacy and control.

A fourth practice involved maintaining my sense of humor.  I have always appreciated a wide variety of humor, ranging from bad jokes, puns and double entendre to witty anecdotes and stories to philosophical musings.  Cancer is anything buy funny, which is precisely why humor has the power to break through the somber mood and fatalistic worldview that so often accompanies the disease.  Using humor became another way of keeping the cancer at bay.  It was a way of saying you may make me sick and eventually kill me, but I’m still going to enjoy a good laugh and a bad joke along the way.

Alongside these practices I could control, there were also beneficial circumstances beyond my control that worked in my favor.  These included the privilege of being a well-educated white male that led to my being treated respectfully and taken seriously by all my health care providers.  In addition, my doctors and nurses consistently combined skill and expertise with compassion and empathy in ways I will never forget or could ever repay. And finally, my privileged status and excellent care played out against a backdrop of strong social support from a dense network of family, friends, colleagues and neighbors.

A final practice that integrated everything else was writing my story as it unfolded. Upon my first hospitalization, I began sending emails to an ever-expanding group of recipients documenting and reflecting upon my disease, treatment and recovery.  Narrating my story for others required me to make sense of it for myself.  The ostensible goal of keeping others informed became a powerful therapeutic prod for my own understanding of what was going on around me and to me.  While my doctors’ ministrations cured my body, my writing preserved my sense of self and a coherent identity.

I eventually sent over 60 lengthy reports to a group of roughly 50 recipients over a 16-month period.  This writing would eventually serve three purposes.  It was a sense-making procedure for me. It was a communication vehicle with my correspondents. And finally, I realized it could be a resource for others in the broader cancer community. With that insight, I did some additional writing about lessons learned and identity transformations and published the resulting account.

As I mentioned at the start, I will never know if any of these practices or circumstances made a material contribution to my survival.  But they maintained my sanity and preserved my identity during the most challenging experience of my life. Regardless of the eventual endings of our journeys, sustaining and nurturing ourselves along the way is a worthy goal in itself.



 

Fact or Fiction? AML Causes & Symptoms


Dr. Daniel Pollyea, an AML specialist, dispels common myths around the causes and symptoms of AML and shares advice so that you can identify credible resources for information. Download the Program Guide here.

Dr. Daniel A. Pollyea is Clinical Director of Leukemia Services in the Division of Medical Oncology, Hematologic Malignancies and Blood and Marrow Transplant at University of Colorado Cancer Center. More about this expert.

See More From the Fact or Fiction? AML Series

Related Resources

 

How is an AML Treatment Approach Determined?

 

Addressing Common Myths About AML Treatment

 

Fact or Fiction? AML Research and Internet Claims


Transcript:

Ross:

I’m Ross Reynolds. Today we’re gonna be debunking some common misconceptions about the causes and symptoms of AML.

And joining me is Dr. Daniel Pollyea. Dr. Pollyea, could you introduce yourself?

 

Dr. Pollyea:

Yeah. Hi. Good morning, everyone. I’m Dan Pollyea. I’m an Associate Professor of Medicine here at the University of Colorado, where I am the Clinical Director of Leukemia Service.

 

Ross:

I wanna emphasize to you that this program is not a substitute for medical advice, so be sure to consult your healthcare team when it comes to solid information about it. But you will get some background that I think you’re gonna find useful. And you might have some questions as we go along.

 Dr. Pollyea, let’s start out with the basics. What are the causes of AML?

 

Dr. Pollyea:

Yeah. So, Acute Myeloid Leukemia, it’s a disease, a cancer of the bone marrow.

And it’s the result of an accumulation of mutation and chromosomal abnormalities that affect the DNA of a precursor cell in the bone marrow, otherwise known as a stem cell.

And those abnormalities accumulate until that cell can no longer properly mature, and it also can’t properly die. And so, a cell like that just makes copy after copy after copy of a cell until it crowds out the whole bone marrow with these sorta useless, immature cells.

And the end result of that is the failure of the bone marrow, which causes all of the problems associated with this disease. So, biologically, that’s sort of what happens to make this disease occur.

 

Ross:

What are some of the myths that you hear from patients that come in and they say, “Oh, this must’ve caused my AML,” but you have to tell them that’s not so?

 

Dr. Pollyea:

Right. So, I mean, this is one of the most frustrating issues for patients and their families after diagnosis. I mean, it’s a rare disease, only about 30,000 cases a year in the United States. And so, trying to associate a rare disease with external or environmental factors is difficult to impossible. So, although there are a variety of exposures that probably contribute to this disease, we have very little understanding of what those exposures typically are or how that all works.

So, there’s a few things that we know pretty well; large doses of radiation, either associated with like industrial accidents like the Chernobyl disaster, or some of the radiation therapies that patients receive for other types of cancer. Other types of chemotherapy that are used to cure other cancers can contribute to this disease in later years.

We know that there are certain precursor conditions that can evolve to AML, so a person with myelodysplastic syndrome, for instance, has a fairly high chance of someday evolving to develop Acute Myeloid Leukemia. But beyond these sort of a few associations, there isn’t a whole lot that’s known or proven.

 

Ross:

Now there is radiation associated with X-rays, and some people think that X-rays can cause AML. Is that true?

 

Dr. Pollyea:

Yeah.

So, I mean, I think a priori no because millions of people get X-rays every day, and only 30,000 people a year get AML. So, clearly it’s not a simple association between getting an X-ray and developing AML. But I think that there is an unknown interaction between environmental exposures and a person’s individual genetic makeup that makes a person more or less susceptible to developing something like AML with respect to exposure to the environment or X-rays and things.

So, while you cannot say that getting an X-ray will lead to AML, certainly there are some people who are more sensitive to the damage that’s done by something like an X-ray. And so, the best course of action is to be cautious and judicious about your exposure to these things, but not to not get these things when they are medically necessary.

So, that’s the challenging balance.

 

Ross:

Here’s something else we’ve heard, that weed killers can be a risk factor for AML. Is that true?

 

Dr. Pollyea:

I mean, I think there’s a lot coming out now about weed killers and their association with other types of cancers. Again, I go back to the limitation we have in that in only 30,000 people a year in the United States get AML. Millions of people are exposed to weed killers.

We’re statistically never going to be able to make a clear association. I think that there are certainly some risks for some people. Whether you’re that person who’s more susceptible to developing leukemia or any other cancer because of exposure to a weed killer is impossible to know.

So, like all of these things, I think the advice we have is you have to live your life. You have to do your best to sort of avoid things that you can avoid that you think would be… Or that may cause problems. But not to let those things prevent you from living a normal life.

I know that’s not a satisfying answer, but at the moment that’s the best answer we have.

 

Ross:

Is formaldehyde exposure another risk factor for AML?

 

Dr. Pollyea:

Yeah. We think that it is, and kind of along the lines of benzene. But, again, we think that those studies that have shown those types of association show it in very high amounts, amounts that most people in this country would not be exposed to. But I do think, or we do think that there is something to that, to formaldehyde somehow contributing to this.

 

Ross:

What’s the difference between a risk factor for AML and a cause of AML?

 

Dr. Pollyea:

Yeah. So, I think risk factors by definition are things that may contribute to AML. And a risk factor for AML by that definition could be walking down the street and having some exposure to radiation from the sun. A cause of AML is something that is a much more solid sort of well-understood factor.

Like I said before, having myelodysplastic syndrome, there is a high chance that that can evolve to Acute Myeloid Leukemia. And if that happens then the MDS, the myelodysplastic syndrome, could be considered or would be considered the cause of your AML. So, very, very different in terms of the amount of evidence that goes into making those determinations

 

Ross:

Is there a genetic component to this? Can this run in a family?

 

Dr. Pollyea:

Yeah. So, this is a disease of the genome.

So, I mean, in a lot of respects it is a genetic disease. But the question is very different when you ask is this an inherited genetic disease? Is this disease due to a gene that I inherited from a parent or could pass along to a child?

For many, many years, the answer from the medical community was, “No.” This was not considered to be a disease that clustered in families or that could be inherited. We now know that that’s not necessarily the case. There are some very rare cases where this does seem to travel in families or cluster in families. And we’re now beginning to understand who those people are and what those genes are.

But the vast majority of people with this disease did not inherit a gene to contribute to it and cannot pass this along to a child. This is a random, spontaneous event that occurred within one person’s own body and is not traveling within family. So, we’re learning more and more about this, but really, the vast majority of this is not an inherited genetic condition.

 

Ross:

You’ve mentioned gene mutations. What mutates a gene? What causes that to happen that could lead down the line to AML?

 

Dr. Pollyea:

Yeah. Yeah. That’s a great question. Most of the time we do not know the answer to that. These gene mutations occur spontaneously, randomly, and we don’t understand why they happen when they do happen.

And I know that’s, again, not a satisfying answer. It’s very frustrating, particularly patients come in, and, “I’ve lived a healthy lifestyle. I’ve done everything right. I exercise. I eat right. How could this have happened?”

These are things that for the most part are out of the control of a person. These aren’t impacted by your diet or your activity levels, what you eat or don’t eat, what you do or don’t do. That’s a real frustration. In the end, in almost all cases we don’t know or understand why these gene mutations or these, I call them mistakes in the body, occur when they occur. We don’t understand them.

And, Dr. Pollyea, someone asked if benzene can be a risk factor for AML.

 

Dr. Pollyea:

Yeah. So, benzene is one of the sort of rare environmental exposure associations that we do have clear associations with AML.

But the level of benzene that a person would need to be exposed to is really something that hasn’t been seen in this country in a very long time.

We’d be talking about like an industrial accident type exposure in almost all cases, so being exposed to a cleaning solution or some other fairly minor exposure to benzene, we don’t think is enough, in most cases, to prompt this disease. But benzene in very high doses, like an industrial accident, yes, that is something that we understand can certainly contribute or cause AML.

 

Ross:                          

Autoimmune diseases, such as arthritis, can they increase the risk of AML?

 

Dr. Pollyea:

Oh, boy. That is a really interesting one. So, there are papers in the literature that do support those associations. And I know in my own practice I certainly see that trend. So, I do think that there is something there. There is a proven association between autoimmune conditions and myelodysplastic syndrome, which I said before can be a clear precursor condition to AML. So, certainly, that is an association that is a possibility.

It can be a little difficult to tease out whether it’s those diseases that are associated with ultimately developing AML, or the treatments that people get for some of those autoimmune diseases. Those treatments can modulate the immune system in certain ways that may, in fact, contribute or drive the disease. So, that’s a difficult thing to tease out.

But in general terms, yes, I think there are some associations. Now not by a long shot everyone with an autoimmune disease gets AML. It’s a teeny, tiny fraction. But I think there is an association there.

 

Ross:

How easy is it to diagnose AML?

 

Dr. Pollyea:

Well, I mean, I think there’s very clear diagnostic criteria for AML. But I guess that doesn’t really answer the question. And we certainly have patients who come to us after many months of frustration without a clear diagnosis.

So, those scenarios can play out. Many times AML’s a very dramatic presentation, so people get very, very sick very, very quickly with extraordinarily high white blood cell counts and suppression of all the other blood counts that come from the bone marrow like red blood cells and platelets.

In those cases it’s pretty clear that there is a type of acute leukemia going on. There can be some difficulty distinguishing Acute Myeloid from Acute Lymphoblastic Leukemia; those are sort of like cousins, but very different and treated differently. So, it kinda runs the gamut. I mean, it can be pretty clear, but it’s sometimes missed, so yeah.

 

Ross:

This is a great lead-in to my next question, which is about the symptoms of AML. What should be the warning signs that this might be something you need to get looked at?

 

Dr. Pollyea:

Right. So, at presentation, the main symptoms are reflective of the fact that the bone marrow, the organ that makes all the cells of the blood, has failed.

So, that can cause severe anemia. Signs of anemia: a white sort of appearance, feeling dizzy or lightheaded when standing, short of breath, weak, tired, fatigue. Those are all pretty clear presenting symptoms for AML. Because the bone marrow also is responsible for making platelets that clot the blood, some people will present with a bleeding complication, or a very subtle rash made up of these particular red dots. We call that a petechial rash. And that rash can come on when the platelet count gets very low.

Sometimes a person will present with an infection or infections that don’t go away or don’t clear because of decrease in white blood cells, the infection-fighting cells of the bone marrow. Those are made in the bone marrow and can fail in the setting of this disease. So, those are the most common symptoms at presentation, symptoms that are reflective of bone marrow failure.

 

Ross:

You mentioned that sometimes the presentation could be very dramatic, and it sounds like the symptoms are very severe, very quickly. Is that always the case? Is that often the case?

 

Dr. Pollyea:

That is the case in, I would say, a minority of times. That’s usually the case. It’s more often seen in younger patients with AML. Typically, older patients with AML have a more smoldering course and a much less dramatic presentation, although this sort of very dramatic and dangerous presentation can happen in older patients, but it’s probably something like a third of the time that those very dramatic and medical emergency presentations occur.

 

Ross:

How important is early diagnosis?

 

Dr. Pollyea:

Well, I mean, it’s crucial. I mean, in particular in those cases where it’s a very dramatic and proliferative diagnosis, or presentation. A quick diagnosis and recognition of this condition is very important because the sooner a person starts effective treatment the better the ultimate outcome is.

I would say in general terms that applies to all AML patients, but certainly there’s some degrees of variation. So, there’s some AML patients that when I hear about their case on the phone from a referring doctor, it’s appropriate to see them next week in the clinic.

So, it’s not always a medical emergency, but we would never, even in those next-week-in-the-clinic patients, this isn’t something that can wait for weeks or certainly months. This is something that needs to be addressed fairly quickly.

 

Ross:

What are the best ways to manage those symptoms?

 

Dr. Pollyea:

Right. So, I mean, at presentation, all those symptoms, the best way to manage those are to start treatment as quickly as possible. So, impacting the underlying cause of this disease is the most important and critical factor to getting a person feeling better because all of these problems stem from the disease in the bone marrow, and so everything else that you do to sort of help a person’s symptoms are Band-Aids when you’re not talking about getting to the root cause.

So, that’s at presentation. Now once we start treatment, there are many potential side effects to any number of treatments. And it all is dependent on what treatment you’re getting and other things about you that will make this a significant problem in some cases. And in that setting, we do have ways that we can aggressively manage a person’s side effects.

 

Ross:

Can you manage all of the symptoms? Or can people still be experiencing symptoms even after they’re in treatment?

 

Dr. Pollyea:

Absolutely. So, a person with this disease, depending on how long they’ve had it and some of the features, may not be feeling back to their baseline self for potentially weeks or months after treatment starts in the best-case scenario. So, that can be very frustrating, but a person needs to sort of be able to continue to have a good outlook and stay positive.

Because we are able in many cases to make a big impact on this disease and return a person to their pre-disease quality of life.

 

Ross:

What are some of the myths that you hear, Dr. Pollyea, about the treatment? Some things that people come in to you saying they think that it helps, but there’s no science to back that up?

 

Dr. Pollyea:

So, myths about treatment, so many people have a lot of preconceived notions about the intensity of a therapy that they’re going to be asked to withstand. And although sometimes we do treat this disease very intensively, that’s not always the case, and now we have some very effective lower-intensity regimens that can be used in a variety of different scenarios.

There are a lot of people who have a lot of preconceived notions about a stem-cell transplant or a bone-marrow transplant and whether or not they would be eligible for this based on maybe what they’ve heard from friends or family, or what they’ve seen in the internet.

And those are often incorrect. And so, keeping an open mind about treatment options, and discussing those in detail with your doctor are really, really important.

 

Ross:

You mentioned sometimes it presents in young people, sometimes in older people. What’s sort of typical?

 

Dr. Pollyea:

This is a disease of predominantly older patients, so the median age of presentation is 68. So, that means that over half of the patients are over 68 years old at diagnosis. So, while this does happen, can happen in younger patients, that’s really an unusual situation. This disease is, like I said, it is predominantly a disease of older patients.

 

Ross:

There are some patients who I understand think that supplements can deal with the symptoms of AML. Is that accurate?

 

Dr. Pollyea:

You know, I mean, I think the supplement question is always a challenge. A lot of these supplements, or most of these supplements have never been tested with the rigor of treatments that we’re accustomed to in the medical establishment.

That being said, I won’t deny that some of the supplements can help patients based on what patients’ experiences are and what they tell me. I think what’s really important is just be very open and honest with your doctor about the supplements that you’re taking or want to take to ensure that there are no sort of unanticipated interactions with treatments.

Because I think most doctors are very open to having their patients care for themselves in the ways that they’ve become accustomed to, and they know their bodies very well, and we’re very open to that. But there are sometimes that a drug or a supplement might have a bad interaction with the treatment.

And so, a good example in my practice is antioxidants. So, there’s a lot of literature, a lot of interest in antioxidants as cancer-prevention treatment.

And a lot of that is not well-established, but still I don’t see much harm. But when it comes time to treating a cancer, that’s a very different situation. When we give a patient treatment to try to kill the cancer cells, many times we’re trying to provoke oxidation. That’s part of how these drugs and these treatments work.

So, if you’re taking those treatments, but also at the same time taking antioxidants, there’s the potential you could sort of be cutting your therapy off at the knees, fighting it with one hand behind your back. So, for the period of time when my patients are getting an active treatment, I ask that they don’t take it antioxidant.

And they can resume that in the future in the hopes of preventing another cancer. But the time to prevent with an antioxidant isn’t appropriate when you’re dealing with an active cancer. So, that’s just one example.

 

Ross:

Fatigue could be a symptom of AML, but there are a lot of causes of fatigue.

How do you differentiate between something that really could be AML and something that isn’t?

 

Dr. Pollyea:

Yeah. That’s a challenge because I think these are, as I said, older patients. And older patients have a lot of other medical problems. And older people get fatigued, just that’s unfortunately part of the normal aging process. So, we would usually make an assumption that a person’s fatigue and diagnosis is due to the leukemia, the anemia as a result of the leukemia.

But as we successfully treat a patient if they are responding based on their numbers and other objective criteria, but the fatigue is not improving then I think that’s where we would start to look at other contributing factors, and there can be many, so having an open mind at that point is important.

But at the beginning, this is such a monster of a disease, it’s so overwhelming, I think the focus is usually on assumption that the fatigue is due to the disease or to a treatment associated with this disease.

 

Ross:

This question: is loss of appetite a symptom of AML?

 

Dr. Pollyea:

Yeah. I definitely see that, hear that, so sometimes people come in and they say that. Sometimes it may not be a loss of appetite, but an extreme weight loss, so a lot of different types of cancer, including AML, can cause that, just basically unintentional weight loss.

A person’s not trying to lose weight. They’re eating what they think is their normal amount and they’re losing tremendous amounts of weight. So, those are both potential presenting symptoms with AML. And loss of appetite, unfortunately, can be associated with some of the treatments for this disease. And taste changes, things not tasting good, can all contribute to that as well, so those are all challenges that our patients face.

 

Ross:

How important is to get a second opinion? I mean, are all doctors like you pretty much on the same page when it comes to symptoms and treatment?

 

Dr. Pollyea:

So, this is a challenge. So, the answer to the second question first is unfortunately, no. A lot of this hasn’t quite been standardized. And some doctors, oncologists, cancer doctors, they’ll predominantly be treating the things that are common: colon cancer, breast cancer, prostate cancer. And they will probably only have a few cases of acute leukemia a year.

And so, their approach to this is going to be different than somebody who spends all day seeing patients with AML and thinking about AML.

So, a second opinion is a very nice thing to be able to do. The problem with this disease is that most times it doesn’t afford that opportunity. So, with other conditions you have some time to go out, read about it, talk to some different doctors, get a good plan together.

With AML, often that’s not a possibility. A person is so urgently sick that you have to sorta deal with the resources where you are. The best recommendation I have there, if you do find yourself in a situation where there’s not a lot of expertise is to ask your doctor to just call somebody in the region or email somebody in the region who may have that expertise.

And most doctors all over the country have that sort of resource or partner that they will go to and talk the case through with them, and maybe a transfer to one of those high-volume centers is appropriate.

And maybe that’s not a possibility or appropriate, but maybe you would benefit from just talking… Maybe your doctor would benefit from talking this through. But in cases where it’s not such a dramatic presentation, then yeah, for sure, I think a second opinion can be appropriate. But this isn’t something that can be sort of drawn out for long period of time.

 

Ross:

You know, when you find out something like this, your tendency might be to jump on the web and start searching for AML. How do you vet those sources that you look at? How do you figure out that their – what would be a sign that they’re bogus sources?

 

Dr. Pollyea:

Yeah. I mean, I think this field is so rapidly changing and the treatment that we have, that I would, for the most part, assume that what you’re finding on the web is not relevant and is not an up-to-date resource. So, the resources that I listed, the NCCN, UpToDate, the Leukemia & Lymphoma Society, I should mention.

A very important resource that has up-to-date information, and they have even phone numbers for patients and their families to call to get connected with the proper people in a particular city, so that is a really important resource. But I’d be really, really cautious about what you find on the internet because things are changing so fast in this field. There’s a lot of outdated and misinformation on the internet.

 

Ross:

Well, then there’s outright scams. One of the things you mentioned before we went on is be cautious if someone’s asking you to put money upfront, or if it’s a nonmedical facility. What are some things that people should watch out for?

 

Dr. Pollyea:

Yeah. So, one of the things that is so important in our area is clinical trials and participating in clinical trials. Patients who opt to do this and receive experimental therapies can sometimes get the treatment of the future, get a drug that’s not currently available through the FDA, but may have a lot of promise.

And this is the way that we fight this disease. We’ve recently had an onslaught of approvals for AML and that’s because the patients being willing to participate in sanctioned clinical trials. So, participating in a sanctioned clinical trial is crucial, and it’s always a recommendation of all leukemia doctors.

When you participate in a conventional clinical trial, you’re asked to sign a consent form that explains what you’re doing and why. There is a confirmation that this has been vetted by an institution’s regulatory board that is prioritizing the safety and well-being of you, the patient. This has been approved by the FDA as a clinical trial. Nobody would ever ask you to pay money. That’s not ethical to participate in a clinical trial. Insurance covers whatever standard of care. And the clinical trial covers anything that isn’t.

So, if you find yourself in a situation where you’re not being asked to sign a consent form, where a clinical trial has not been reviewed by a regulatory board, where your doctor is not a leukemia specialist, where the FDA has not sanctioned the treatment, all of those are alarm signs.

Because there are people out there that are preying on patients in a desperate situation, a very difficult time in their life, and giving them sort of false hope and leading them down paths that are not legitimate.

One easy thing to do to sorta check to see if a clinical trial is legitimate is to go onto clinicaltrials.gov.

This is a resource set up by our national healthcare system that now feeds in every legitimate clinical trial from all over the world, needs to be registered on clinicaltrials.gov. So, if you can’t find your clinical trial on clinicaltrials.gov, I would have a lot skepticism and caution about that.

 

Ross:

Like what advice do you have for people when they’re first diagnosed? What are the first things they should try to do?

 

Dr. Pollyea:

Yeah. I mean, that reaction is totally normal and natural. I mean, many times these people are perfectly healthy or have been perfectly healthy, and this news is a complete shock.

And so, it is normal and appropriate to have some period of grieving for the healthy life that you are losing. But I would also, while giving yourself that time to grieve, first, draw on your support system, your family, your friends. Allow them to help you. Accept that assistance that they have. And to be optimistic because we are getting so much better at treating this disease.

I had mentioned before, there has been an onslaught of approvals for drugs in this area the likes of which hasn’t been seen in decades. We have new tools and weapons in our arsenal that we couldn’t have dreamed of even a few years ago.

We in our community are very excited and hopeful about the future and we hope that that will translate ultimately to patients, but being depressed or being down, being scared, all of that is normal.

All of that is expected. Anyone would feel like that. Allowing yourself to have those feelings and emotions is important, as long as it doesn’t get in the way of doing what you need to do to fight this disease.

 

Ross:

It sounds like you’re hopeful about new treatments for the disease. How about a cure? What’s the science? What’s the medical science say about that? Are we getting any closer to that?

 

Dr. Pollyea:

We are getting closer to curing this in more cases. So, like I mentioned before, as bad as this is, we can already cure some subsets of patients. There’s one type of Acute Myeloid Leukemia called Acute Promyelocytic Leukemia, APL. It’s an uncommon form of AML, less than 10 percent.

But we can cure close to 99 percent of people with APL. And APL, 15 years ago, was universally the worst form of acute leukemia to get. So, that dramatic 180 that we’ve seen in APL, we are hoping to translate into other forms of AML.

Some other forms of AML have cure rates as high as 50 percent, 60 percent, 70 percent in the right setting. Sometimes we can cure patients with a stem cell transplant fairly reliably. So, we are very, very hopeful about our ability to continue to make progress and cure more and more and more of these patients. That’s the future that we see.

 

Ross:

Dr. Pollyea, thank you so much. And thank you so much for ending on such a positive note. We really appreciate it. And thank you for joining us for this program today.

To learn more about AML and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Ross Reynolds. Thanks for joining us.

Coping With the Emotional Side Effects of AML

A dynamic panel discusses the important aspects of care for AML patients, with a focus on the emotional side effects, research on new treatments underway and finding suitable clinical trials.

Downloadable Program Guide


Transcript:

Beth Probert:

Hello, I’m Beth Probert, and I am a patient advocated and ambassador with Patient Power.

I am also an MPN patient. Thanks for joining us for this Patient Empowerment Program in partnership with The Leukemia and Lymphoma Society. Today, our program is: Coping with the Emotional Side-Effects of AML. And we are joining our AML community.

We’re gonna focus on where we’re headed with treatment of Acute Myeloid Leukemia; what patients can look forward to in the coming year.

We will also answer questions that you can submit to AML at patientpower.info. And please note that we cannot provide specific medical advice over the internet. And it wouldn’t be fair to you. We always recommend that you seek care from your own doctor or AML specialist, and that’s how you will get the best treatment for you.

I’d like to start now and introduce our panel. And we’ll start off with Dr. Thomas LeBlanc. A medical oncologist, palliative care physician, and patient experience researcher from Duke Cancer Institute. Welcome, Dr. LeBlanc.

 

Dr. LeBlanc:

Hi, thanks for having me.

 

Beth Probert:

And I would like to introduce Michelle Rajotte. She is the Associate Director of the Leukemia Lymphoma Society’s Information Resources Center. Michelle has been with LLS for 13 years. Hi, Michelle.

 

Michelle Rajotte:

Hi, good to be here.

 

Beth Probert:

Thank you. And last but not least, I’d like to introduce our patient advocate today, James Bond. And James has survived Multiple Myeloma for 27 years, and AML for the past 7 years. James and his wife, Kathleen, have shared their story in 29 states. And patients can contact him directly at his email, which is Jim.Bond48@gmail.com.

So, thank you for joining us today, Jim.

 

James Bond:

Happy to be here.

 

Beth Probert:

Great. Well, Dr. LeBlanc, I would like to start with you. Tell us a little bit about your background in AML and palliative care, please.

 

Dr. LeBlanc:

Sure. So, by training I’m an oncologist. But when I went through my cancer care training, I realized that oftentimes we fail to really attend to some of the issues that are most important to patients and families. And those might be things related to symptom burden, quality of life, emotional well-being, communication, understanding of prognosis.

And so, I ended up pursing additional training in palliative medicine where those types of issues really are the focus. And in doing so, got a sense that really adding specialist palliative care to cancer care and blood cancer care particularly, really could improve many aspects of the experience for patients and families.

And ultimately that is what my clinical practice and research have come to focus on. But in my clinical practice, I largely see patients with myeloid malignancies, including Acute Myeloid Leukemia and some related conditions.

 

Beth Probert:

That is so interesting and very unique because very often we see our doctors and we don’t get the whole palliative side of it. So, I can honestly and personally say that that is just a wonderful added bonus. Thank you.

And Michelle, can you tell us a little bit about your role at LLS, and really what the goal of the information resource center is?

 

Michelle Rajotte:

Sure. So, I’m part of the Information Resource Center at Leukemia Lymphoma Society. Which, The Leukemia and Lymphoma Society’s main goal is to help find a cure for Leukemia, Lymphoma, Hodgkin’s disease, Myeloma, and improve the quality of life of all patients and their families.

And IRC is apart of that. So, basically, what we do is – it’s staffed by information specialists who are master level, either social workers, nurses, or other healthcare professionals who’ve been trained in blood cancer. And we can do anything from answer questions, provide disease information, help with clinical trial searches, find different support resources, refer to other organizations if we need to for other resources. But really, it’s anything that someone needs in the moment.

So, we’ll talk with them over the phone, through email, or through chat online, and we figure out what it is that they need based on talking to them, or whatever they provide to us. And then, provide them with the resources and support they need.

 

Beth Probert:

Wow. And that is just invaluable. And we definitely need to bring focus to the cancer patients and what your department could ultimately provide to them. Thank you.

So, Jim. You are a long-time survivor. How has your cancer diagnosis impacted you emotionally?

 

James Bond:

Well, it’s been like riding a roller coaster. My care-giver wife, Kathleen, Kathleen is sorry she can’t be joining us today. But the lowest point, of course, was getting diagnosed with a deadly incurable blood cancer. My first one, Multiple Myeloma. And then the second one, AML, many years later.

And so, what we tried our best to do is, to try to even out that roller coaster ride emotionally. And, I’ll give you an example, after 10 years of dealing with Myeloma, I was told, Jim, there’s nothing left that can help you, you need to go to a hospice. And that was obviously crushing.

And what we tried to do is pull each other up and say, “Look, we’ve been through tough spots before.” And we figured out that just rely on the doctors, rely on our own research ability, and they’ll be something coming up. And we were able to figure out, hey, there’s a clinical trial that was mentioned to us, and within a month of being told to go to a hospice, we were out of town in a clinical trial, and within two weeks, I was told, “You’re in remission.”

So, that was a tremendous high. And again, what we try to do when we get really good news is pull each other down and try not to be so excited, but we try to even things out. And that’s very difficult to execute, but for 27 years now, we’ve had a good deal of experience. There are a few other tings we do emotionally, we say, “Look, let’s do all we can, and then let’s not look back and second guess ourselves.”

And even to make it more normal, we cut off all cancer discussions with ourselves, ideas, or with a family member at 8:00 p.m. our time. We say, “You know what? Let’s just do what we’re gonna do at night, and let’s defer that to the morning.” That tends to let our emotions calm down and let us live more normal lives. At least in our minds.

It has not been easy. It’s been very difficult and emotionally at times, we’ve actually played a role of trying to lift up the medical team who, the AML diagnosis in particular, they explained to me, “Jim, you’re 64 years old,” When I got AML, that was seven years ago. They said, “Your chances of survival are not good. The only way you can live is through a fourth bone marrow transplant. And this one has to be not from your matching sister, but from an unrelated donor, if we can find one.” 

So, they really encouraged me to consider just hanging up, but our approach, and this helps us emotionally is, no, we’re gonna treat this thing called cancer like a problem. We’re gonna put it in front of us, and we’re gonna deal with it as analytically, or unemotionally as we possibly can. And lo and behold, the doctors, as they’d come around in my, I don’t know, 10-week stay in the hospital, whatever it was, they would keep trying to say, “Jim, don’t get your hopes up. This might not work out.”

And it did work out, and we found ourselves much better off by, I do my favorite thing, and that is, I make myself exercise each and every day. And sometimes that exercise is not much, it’s walking with my IV pole around the floor section when doing a transplant.

Or it’s walking on my treadmill on snowy icy Ohio days like today. But that helps me emotionally because it gives me something that’s not cancer, it’s quiet time to think, and it really led to something that’s been just magical in terms of helping both of us emotionally.

When I had to leave town to do the clinical trial, my wife, Kathleen, got to thinking as a long-term volunteer of the American Cancer Society, she realized that there are not enough people in the country aware of these things that the ACS has called, “Hope Lodges.” So, she founded, launched, and leads, to this day – this was 13 years ago, she launched the first one. And I was not a cyclist, but I saw a link between the exercise that I think is so vital for me emotionally and physically, and this bike ride. So, I decided to buy a bike and trained. And I’ll be darned, I’ve ridden it every year four days, 328 miles from Cleveland to Cincinnati.

 

Beth Probert:

Wow, well that is really inspiring.

 

James Bond:

Thank you. And that helps me tremendously emotionally because that training and riding takes up a good three and a half, four months of my year, and I look forward to that, and the fundraising is tremendously exhilarating because I get to hear from people that I don’t hear from that often.

 

Beth Probert:

Yes.

 

James Bond:

So, the key there is emotionally, I think, is just having a long-term plan, and not letting –

 

Beth Probert:

And Jim, I’m just gonna jump in really quickly, this is amazing information. So, hold that thought, we are going to jump on some of the thoughts you said, and I do want to say real quickly, I love the, “We” in that. We.

 

James Bond:

Oh, absolutely.

 

Beth Probert:

And we’ll click back onto that. So, I’m gonna hop over now to Dr. LeBlanc. And could you go through, with your vast experience, what are the key emotional side effects that you see your ALM patients facing day to day?

 

Dr. LeBlanc:

Yeah, this is such an important question, and it’s one that we don’t ask often enough, and we don’t talk about these issues very often, unfortunately. So, I’m really excited that we’re having this webinar, first of all. And I’ll tell you, it’s important to recognize as well, every patient, every person is different. So, there is not one quintessential AML experience. That’s really important to recognize.

But at the same time, when we have studied this issue and interviewed patients, and care givers, and family members, there certainly have been some common themes that have come through about people’s experiences. And one of the one that is, I think, particularly important to recognize is the sense of shock at this diagnosis. Now, acute leukemias, we call them acute because they tend to come on very quickly and suddenly. 

And many of the patients we see will say things like, “I was fine three weeks ago. And now I can’t even walk up a flight of stairs.” And, “I’m so tired, I’m taking naps, this is not like me. I usually run marathons, and now I can only run a couple miles, something is going on.” And this really degenerates, for many, people over the course of day or a few weeks.

And sometimes it means they end up urgently in the hospital and are told, “You can’t leave. Something’s going on, we don’t really know what it is, but we’re concerned. You might have leukemia.” And if they’re not at a large medical center, they may get shipped off hours away from home to a place that’s not familiar where they don’t know anyone.

So, that shock and suddenness of the diagnosis makes everything else much more difficult, and it sometimes creates, even, social isolation related to where AML is treated. Where it tends to be treated more so at academic centers than it is in the community, although, certainly, some of these treatments are provided in the community.

But patients getting high-dose therapies do tend to come to large research centers. So, we’ve certainly seen that issue impact many patient’s experiences. The other one that comes up quite often, that really compounds the decision making and the emotional difficulties, is the issue of uncertainty. So, unlike many cancers, we really don’t know what to expect when a person is diagnosed with AML. And everyone asks, “Well, what stage is this?” and we don’t really have stages for this disease.

We, certainly, have ways that we can try to get a sense for what we might expect for the patient who’s sitting before us. And we do all kinds of fancy testing, and we talk at length about those issues, but at the same time, we really can’t say what’s going to happen to you, my patient sitting across from me who I’m trying to help guide through the process.

And there are actually a lot more risks associated with Leukemia treatments as you heard Jim talk about. A stem-cell transplant is a difficult and risky process, and sometimes that’s part of curing AML, or hoping to cure AML. But even high-dose chemotherapies in the hospital, some people actually do have really difficult complications, and even can die from those treatments, and yet, those are the treatments that usually are required to cure a person.

So, we have to have these difficult decisions made sometimes under a lot of distress emotionally, and amid the suddenness of this diagnosis, where we say, this is probably the best treatment for you, and it gives you a chance at cure, but it’s not a guarantee. And some people end up not making it out of the hospital. And usually what happens is, that’s just such difficult information. Many folks shut down and they say, “I don’t know, what should I do. Tell me what to do.”

Or they’ll turn to a family member or a friend who might or might not be around and available during that difficult time, especially if they’re in another city away from home. So, these are some of the things we’ll commonly see when patients are newly diagnosed with AML.

 

Beth Probert:

Wow. That is very intense. And there’s obvious emotional connections. And sometimes we hear someone’s diagnosed, and we completely forget that emotional side. So, I wanted to ask you, as well, you’ve been involved with research into the relationship between the emotional stress in AML patients and the overall prognosis. Could you please explain how the study was conducted, and what were some of the prevailing results of this study?

 

Dr. LeBlanc:

Sure. So, we did a longitudinal study of patients with AML who were being seen and treated on our in-patient service. So, these were mostly patients getting high-dose chemotherapy who would be stuck in the hospital for a month or even a bit more.

Like Jim described, getting these really intensive treatment regiments. And this was a study basically aimed at helping us better understand what people go through when they live that. And certainly, I’ve seen that in caring for many patients with AML, as have our nurses, and other members of the cancer care team, but actually, there has been very little formal, objective study of the patient experience with AML and related blood cancers.

So, what we did is we actually surveyed patients using validated instruments, and we assessed their symptoms, their quality of life, their overall distress levels, and in addition, we assed their understanding of their illness. Their understanding of what we call, “prognosis,” The idea of what the likely outcome of the treatment or the disease is going to be. And we did all of those – that whole battery of assessments every week when they were in the hospital, and then when they were out of the hospital, we did that every month.

And we followed patients for six or even upwards of 12 months, and different things happened. Some people went into remission and were cured, some people had relapses, some people went into transplant, some people had transient remissions, or even multiple relapses, got additional treatment. And by following patients over time, we were able to develop a profile of the patient experience with AML and look at different versions of that. Including, what people understand about their illness, and how that relates to their overall emotional well-being.

 

Beth Probert:

That is amazing. And was there something that just jumped out real quickly as far as the largest response rate you saw when people were taking care of that emotional part?

 

Dr. LeBlanc:

Well, the concerning thing that we found, which unfortunately is an issue across all of cancer care is that many people who are diagnosed with AML, especially when newly diagnosed, really don’t have a good understanding of the likely outcomes.

And it’s certainly not for lack of talking with patients and families about these issues, but it probably is a manifestation of the fact that this usually happened suddenly, as I mentioned, and it’s so emotionally overwhelming and difficult that it’s actually really difficult to contextualize the information that’s provided. And we, I think, end up overwhelming a lot of patients and families with so much information, that sometimes there’s a bit of a forest and trees problem, where maybe the most important factors don’t always get explained clearly or don’t come through well.

And we don’t always go back and check in about whether we did a good job of explaining things, which is unfortunately a shortcoming that most of us struggle with in taking care of patients. Communication of complex information is very difficult. 

So, we found that many folks didn’t understand, for example, that the treatment they were receiving maybe wasn’t likely to yield a cure, which is true in some instances of AML. Or they might not have had a very good understand of the risks. So, one study, for example, suggests that AML patients may actually think the treatment is way more risky than it really is. And is that prompting some people to not receive intensive treatments that maybe could be the right choice for them and the most helpful for them. So, that was the one main interesting finding.

And then, related to that, unfortunately we also found that many patients who do come to more accurately understand the outcomes that are most likely with their particular situation, some of these are better than others, everyone’s different, the more accurately people understand their illness, there tends to me more emotional distress and sadness. Perhaps realizing that this is a very difficult disease to treat. And unfortunately, when we were doing this study, this was before we have eight new drugs approved in the last two years. 

So, hopefully some of this has changed. But that’s why we’re having this webinar, and why we need to talk more about these issues.

 

Beth Probert:

Absolutely. So, now, Michelle. I definitely see that your role at LLS plays a huge part in this. And in your experience, how do you deal with this? What resources seem to be the most effective that you can provide patients in coping and the emotional side of this cancer diagnosis, and also, taking parts of what Dr. LeBlanc just said, I would love to hear from you now and what your role is.

 

Michelle Rajotte:

Sure. I think it’s different for different people. We’ll talk to people who want to know everything, and we’ll talk to people who just say, “Just tell me the basics, I can’t get overwhelmed right now.” And it also depends on where they are in their cancer journey. Are they just diagnosed; are they relapsed? I think a big piece is being able to talk to other people who can relate to what they are going through.

So, other people who have been through this already and have gotten to the other side and feel like, okay, it can get better, there is hope. Here’s some things that might help. Because unless you’ve been through it yourself, I don’t think you can completely understand. You can empathize, you can be there for someone, but your friends and your family may not be able to give you that support that someone could that has been through it.

So, for example, at LLS we have the Patty Robinson First Connection Program, which can help over the phone to be able to talk with someone. And they may be across the country, but they may be very similar in background to you and be able to answer some questions that you have while you’re going through things.

There’s an LLS community where you can go on and talk with people. We have a lot of online support groups. There are online chats that are set up to be able to talk with, again, others, it could be across the country, they’re people you may have never had the opportunity to meet. Or if you’re not doing well, or you’re in the hospital, or your immune system’s compromised, you still can reach out and get that support.

And it’s not going to be something where you physically have to go somewhere, but there’s those options too. Or someone may not be ready to go sit in a group and talk about what they’re going through but can sit in front of a computer and just say, “All right, I really do need to talk to someone.”

Also getting professional support from a social worker, or a counsellor, or just anyone who can help you get through this because it is extremely stressful. And some people think, “Oh, I really don’t need that.” But it may be exactly what you need just to help you get through it.

Also, pulling in friends and family. And again, sometimes they may be more stressful because they don’t completely understand, and even though they’re trying to help sometimes it may have the opposite effect, but the intention is there, and it’s good to have them there, even if it’s just to drive you to a doctor’s appointment. And help you understand what the doctor’s talking about.

 

Beth Probert:

Wow, that is very impactful. It sounds like you really give the patients a complete tool kit as far as how to have these conversations and the unbelievable amount of resources that are available to them. So, that is invaluable. Thank you, Michelle. We’ll get back to you again.

And Jim, going back to you, did you reach out to your doctor in regards to this whole emotional turmoil, and you said earlier the, “Roller coaster.” Was that a talking point with your doctor, by the way, on how you’re feeling and how to cope? What direction did you take when you were first diagnosed, and was your doctor part of the conversation?

 

James Bond:

Well, we’ve been very blessed, very lucky. My first doctor who diagnosed me, he really helped me by answering this question that I asked.

[00:27:30]

And asking questions is a good way for me to relive stress and gain information, like the kind of information that Beth and Tom talked about.

When I was new to blood cancer, I said, “Doctor, now, if you were in my shoes, whom would you have treat your case?” And frankly he was shocked because he was at a leading cancer institute in my hometown here, in Cleveland Ohio, and he gave it real thought. And his compassionate answer blew me away. He said, “Jim, the professor who taught my blood cancer course at the medical school works in another hospital. Another leading cancer institute here in Cleveland. And if I were in your shoes, I would go to him.”

Now, what I did – and for 10 years, until he retired, that man helped us, my wife and I, emotionally and medically in more ways than I could ever describe. 

An 8:00 phone call one night, and which we had never gotten from him, his name was Bob and of course, it’s a doctor, it’s an oncologist, I’ve got a deadly cancer, he’s calling at night. I’m thinking, “Oh, my god. The world’s coming down.” He really relieved our stress, he said, “Jim, those shoes you had on at your last appointment, may I ask you where you got those?”

So, like you said, Tom, each case is unique, and in our case, stress has been relived in some very unusual ways. I got in a car accident after my first of four stem-cell transplants, and my wife was having real problems with stress because now I was in remission and seemingly home free until it came back five years later, but she was really stressed out until I had a car accident where, not my fault, but somebody t-boned me and it really was a tough accident.

I was okay, but the car was wrecked. But when I called her to tell her that, she flipped out. And all this pent-up emotional stress she was going through came out, and it manifested in her yelling at me, how could I possibly have an accident after all we’ve been through? And the thing is, she caught herself, she listened to herself, and she realized, oh my gosh, what’s the point in getting yourself all in a knot over your incurable deadly cancer? You can get taken out by a car accident as any time. Things like that.

 

Beth Probert:

Absolutely. So, she really put it in perspective for you, didn’t she?

 

James Bond:

It really did. It really did. It just happened, it was coincidental that it happened, but it did. And so, we’ve used that. 

Another thing that really helps us with stress is, and this is gonna blow some people away, but the longer we’ve survived with these two cancers, the more we’ve gotten asked to share our story around the country. And if fact, in two countries overseas.

And here’s the thing. We realized from the very first story telling we did in our home town, how much telling our story helped us emotionally. We looked at each other when the couple left our house and we realized, oh my gosh, just sharing our story and the roller coaster parts of it, not the technical parts, but just the emotional part, that really helped us. And so, we welcome other opportunities, and we encourage other survivors, whether it be short-term or long-term survivors, to consider the kind of things that the LLS has, and other organizations that get us out there, get people out there to share your story. It is very helpful for us. And that was a huge surprise to us.

 

Beth Probert:

Well, that is wonderful. And Michelle, I’d like to come back to you for a moment. Do you have resources that you can provide to caregivers and patients with AML, that if they do want to share their story, and is that part of what you do, as well?

 

Michelle Rajotte:

Yes. That is part of the Patty Robinson First Connection program. What it is, it’s trained patient volunteers and family members who’ve been through this, who then want to be able to reach back out and help others who are going through it now. So, that’s one of the things they can do. They can volunteer at their chapters, and there’s always a way to get involved that way. There’s things on our website where people can share their story. There’s lots of different things. On the LLS community, there’s a way for them to be able to post what they’ve been through. There’s blogs that we do. There’s tons of different things. And as far as the care giver, Jim, you bring up a good point, they are going through a lot of stress, as well. And they need just as much support.

And we do have a lot of good caregiver resources now. We have a caregiver workbook that we can send out that has everything you could possibly need as a caregiver to know. And it’s divided into sections, so it’s not overwhelming, but it’s a way to have a roadmap to try to figure out, okay, what do I do? Because just like the person who’s been diagnosed, the care giver gets thrown into this and doesn’t know, what do we do; where do we go; what questions do we ask? I don’t even know where to start.

And a lot of times that’s the question we get at the IRC is, “I’m calling you, but I don’t even know why I’m calling you because I don’t even know what I’m supposed to know.” So, it’s really helping people try to figure out, what is that next step? And that’s really all you have to focus on. If you try to look at the big picture, it can be really overwhelming. But if you can get to the next step, that’s something that’s doable.

 

Beth Probert:

Wow, that’s wonderful to know you folks do provide those resources. Thank you.

So, Dr. LeBlanc, I’d like to shift over to managing fear, anxiety, depression. So, you mentioned a few times that being diagnosed can be so overwhelming, and we can’t ignore that this could lead to anxiety and depression. What sort of things do you recommend to your patients to allay these fears, and to put into place in their life in dealing with this? It’s obvious that for most people it is going to lead to the anxiety and depression.

 

Dr. LeBlanc:

Yeah, this is such an important question, and it’s a really difficult one to address. Most of the time, I do recommend that people talk about it. And sometimes that’s the most difficult thing to do even though it sounds obvious, but it’s often the elephant in the room.

So, many times, the doctors and other clinicians seeing patients with AML and other cancers are just so incredibly busy and also fixated on all of the medical details, and the labs, and the scans, and other treatments, complications, doses of chemo, all of these things that we need to be focused on, of course, that we forget about the person, and the way that they’re struggling with these issues.

And it’s not that we don’t care or that we’re bad people or anything, it’s just that’s never the number one priority when you have to get all of the details straight to make sure the person gets the right treatment. I try to ask, but sometimes we don’t do this. So, for example, if there are other clinicians listening and wondering how to do this, one thing that I do is to just say, “This is really difficult to go through. How are you holding up? What do you look to for strength?”

And I will ask the person there with them. Usually patients aren’t there alone, and typically the person who’s with them is the person who’s really helping them keep it all together. Whether it be a spouse, a family member, a caregiver, a friend.

And I usually turn to them and also ask them, “How are you holding up? What are you seeing? What is the patient not telling me?” You know? What are they going through that they’re – sometimes people will put on a brave face for the doctor and they won’t tell me how much they’re suffering at home, and I really need to know so that I can help.

So, really the best recommendation is open and honest communication. And the other great one is to seek out resources like the ones we just heard about. I sometimes will encourage patients to seek out a family therapist, a psychologist, somebody who they could see in the cancer center, a social worker, someone who they can sit down with for an even longer period of time and just talk about how difficult this experience is. And just talking about it sometimes is really some of the best medicine, honestly.

 

Beth Probert:

Wow. Yeah, I love the tie in to with making sure that the caregiver is doing okay, as well.

 

Dr. LeBlanc:

Yes.

 

Beth Probert:

We often look at them as a pillar of strength and forget that they need those resources.

And one of the things that I personally feel is really really helpful, and I’ve heard from the AML community as well, is the mind, body, soul; exercising, meditation. And Michelle, I wanted to ask you, is that something that, when you talk about resources, that your department provides? Do you find that that’s a very often asked question, and/or it’s a topic that you like to recommend to patients?

 

Michelle Rajotte:

We get a lot of questions about, what can I do? How can I help myself get healthier, or stay well? Or how can I help myself get stronger, or what can I do? And I think a lot of it is, you feel very powerless when you’re diagnosed, and you really don’t have any control. So, if there’s something you can do to feel like you’re taking part in your care and making decisions about some things you want to do, that’s great. We always say, “Check with your doctor to see what’s okay; what’s safe for you to do right now depending on how you’re doing.”

But we have a lot of resources on nutrition, we have a nutritionist that can do a consult, either over the phone or online through email. We have a lot of different resources, and webcasts, and podcasts, and videos, and we have a ton of resources.

It can be a little overwhelming just to go on to the website and try to figure out, okay, what do I look at? Where do I go? So, I would encourage them to call the IRC. We can walk you through, depending on what it is that you’re looking for in the moment, where to find it. How to bookmark it, so you can find it later.

But again, I think it’s really important to discus it with your doctor to see – obviously if you wanna go for a walk, and you’re okay to do it, that’s great. But if there’s a chance that your platelets are very low, and if something can happen, then you gotta check with them about that too. So, we’ll get an idea of what they can do, but we always send them back to the doctor, make sure whatever they decide to do, whether it’s supplements, again, check with your doctor because they can interact.

But anything they want to do to help themselves get stronger or take care of themselves is always a positive.

 

Beth Probert:

Wonderful. And, Jim, I’d like to ask you to stay on this topic for a minute. Could you give any advice about support groups?

 

James Bond:

Yes.

 

Beth Probert:

Is that something that you found to be a great resource in dealing with this kind of anxiety and depression?

 

James Bond:

Yes, I think support groups are for people who want to go to a support group. Put yourself back 27 years ago when we first we introduced to blood cancer. There were not a lot of support groups available. And we started out with keeping it more to ourselves and our family, and then as we grew comfortable with living an managing the fear, the risk, the anxiety, our circle spread out. But it really was not until we got invited to share our story that our eyes were opened of the power of support groups. And we could see it happening.

One other thing that, Tom, I’d like to mention to you, one of the most effective way to manage fear for my wife and I was late one Sunday night lying in week number six, or something, in the last transplant for AML, and I’m on the ropes, I’m in tough shape. And the phone rings, and it was my myeloma doctor from Boston where we go twice a year, his name’s Paul Richardson, he’s an outstanding, compassionate doctor.

It was Paul, and Paul said, “Jim, I’ve just talked to your wife Kathleen at her home,” she had just left for the night. And he said, he said to her what he then said to me. He said, “Jim, I know you’re in a tough spot, but I want you to know, that we’ve got other patients here at Dana Farber, who have been through exactly what you’re going through, myeloma followed by AML, bad, bad prognosis.”

And he assured me that I could do it. And, Tom, what that doctor’s phone call meant to my wife and I could have been the difference between getting through this thing, and not getting through it. Giving up, and not giving up.

And we really believe it’s because our doctors have taken the time to help us build a relationship with them. Knowing how busy they are, and how many patients they have, we found the world of oncologists and the nurses and the others, very compassionate people. And it’s worth that time to build that relationship whether it’s your ongoing doctor, or one that you go out of town for a second opinion with, those relationships mean everything. And the doctors who are willing to take their time, when it’s not really on the clock and help their patients, they are doing tons and tons of good for the world that we live in.

So, we’ve got some other techniques, but those are the things that really stand out to me in terms of managing in this area.

 

Beth Probert:

That’s wonderful, Jim, and it circles right back to you, Dr. LeBlanc, when you introduced yourself and you told us that there is just more than coming to the doctor, and reading the chart, and giving the blood results. It’s definitely very impactful. And what you spoke about earlier about how you bring in the palliative care and the emotional care. And on that note, I know this is a little cross-over, but can certainly add to anxiety and depression on everything that we’ve talked about, Dr. LeBlanc, but do you encounter, through your care and conversations with clients, their anxiety over the financial part of care? Is that something that you hear often?

 

Dr. LeBlanc:

Absolutely. The idea of financial toxicity, sort of like other kinds of systemic toxicities you would have from chemotherapy, it’s just as real as a patient who gets neuropathy from their chemo. And in some cases, may be more crippling.

One of my colleagues here at Duke is a leading researcher in this area, and he’s taught me a lot about this, and unfortunately, I’ve seen it a lot in my clinic. And as we are fortunate to have a number of new therapies available for AML and other diseases like multiple myeloma, the unfortunate aspect of this issue is that many of them are pills, and may states do not have parity laws in place that require insurers to treat pills the same way as they do chemo therapy that you would get in an infusion suite.

North Carolina is unfortunately one of those, where I practice, where we still don’t have a law. 

And that’s sometimes means I’m talking to a patient about an exciting new therapy, and then I find out that their monthly copay is going to be $3,000.00, and who can afford that? That’s just the copay amount for the patient just for one month of medication. This is, unfortunately, happening a lot. And thankfully, there are many resources that we can engage to help patients with these issues, but it is an increasing problem as medications are more sophisticated, they also have gotten much more expensive.

 

Beth Probert:

Yeah, and we hear this so often. And, of course, Michelle, I’m sure you’re hearing this, as well. And your department can direct people to the appropriate resources?

 

Michelle Rajotte:

Yes. It’s something we hear every day, unfortunately. Like Dr. LeBlanc was saying, we’ve got all these great new treatments now, but so many of them are oral, and a lot of patients, if they’re on Medicaid/Medicare especially, their copay is extremely high.

We do have copay assistance through LLS, we will also refer people onto other organizations that have assistance if we know of them. So, anywhere we can get people to get the help. We also do a lot of advocacy on that end, and we’re in Washington a lot and we’re sharing a lot of patient stories, and we’re trying to get the word out there that we shouldn’t have these barricades to treatment. We do all this research, we find all these wonderful treatments, and then people can’t have access to them. And that shouldn’t be.

So, that’s one of the things, along with the research and the patient assistance we have, we also focus on the advocacy part, and making sure that the oral parity bills are passed in hopefully every state. And that things are little bit more on an even plane, so people can use these wonderful treatments that are coming out.

 

Beth Probert:

Wonderful. And Michelle just hit on treatments, so Dr. LeBlanc; I would like to now go back to you. 

And could you tell us, in regard to treatments, advances in clinical trails for AML, what’s happening in research and should patients be hopeful?

 

Dr. LeBlanc:

Yeah, it’s really a very tremendous time in cancer care and in biomedicine in general. As I mentioned earlier, we had, if I remember correctly, eight new drugs approved for AML in the last two years. And we had been mostly using the same treatment for patients for the prior 40 years. The seven plus three induction regiment was developed in the ’60s or early ’70s, and mostly that’s the same regiment or related ones to it that we’ve been giving to people when we give them high-dose therapies for this disease.

Other things have improved during that time, as well, that are really improving outcomes, so we have much better supportive care medicines. We have growth factor injections that work better. We have better antibiotics. We have anti-fungal medicines that work a lot better.

So, when you add those developments, even to the old chemotherapy, that had improved outcomes prior to this spirt of approvals in the last two years, but now, especially, we really are in a new ear of how we treat AML. And now, we need to actually molecularly and genetically profile each individual patient’s leukemia, so that we can best know how to treat their disease because at this point, we have several testable targets that we might then prescribe a medication to address in an individual person’s case of AML. So, it’s getting more complicated, at yet at the same time, there are many more options, and it really is a time to be very hopeful about how things are going.

 

Beth Probert:

That sounds so encouraging. And Michelle, going back to you. How can you lead clients and their care givers to these clinical trials that are on the horizon? 

And can you talk a little bit about what that process looks like?

 

Michelle Rajotte:

Sure. If someone reaches out the IRC, we do have a group of nurses who do clinical trial searches specifically for blood cancers. And it’s not just, we’re gonna hand you a list as say, “Here, go talk to your doctor.” They will help through the process. So, they’ll really in-depth dig, and try to find trials that might be an option. Have you go back to your doctor, but then walk through it with you to help you get into that trial.

Because there’s so much research now, it’s wonderful, but it’s also really overwhelming if you try to do it by yourself. And a lot of them are more focused trials now, so you have to know what kind of mutations you have and that kind of thing. So, it’s a partnership where there’s a form that you would need to fill out for us to have that information, and then we help you walk through that process of, is there a trial that’s out there for you; is it something that’s appropriate for you, along with your doctor. And then, how do we help you make sure that you can get through the whole process.

 

Beth Probert:

Wonderful. What a fantastic resource. Thank you.

So, I would like to take a few questions that we’ve received, and, Jim, I’d like to hear your feedback on this one. And the viewer asked, “People keep asking me how I’m doing, and it just makes me worry more.” Do you have any advice, Jim, for people to tell those that love them and just want to help them that all these questions are causing anxiety, what would you suggest, Jim?

 

James Bond:

Yeah, a couple things that I’ve found useful. I explain to them I just got done with playing nine holes of golf, or I just got done exercising, and I’m quick turn it back and say, “How are you doing?” and try to get as much out of the other person, so that they understand that I’m comfortable in my skin, and I’m not stressing out or how things are going.

But it’s easy for people to understand that, hey, this guy’s got an incurable deadly blood cancer, or two, and we worry about him. So, I try to just loosen up, and turn it back on them, and hopefully they get more reassurance that, hey, the guy’s not stressing out, he’s okay. But you know, once you do all you can do, the rest of it is just fate, luck, whatever. So, that’s what we try to do.

 

Beth Probert:

I love that response. And people mean well, but putting the focus back on them is just fabulous. That’s really great, thank you, Jim.

 

James Bond:

Oh, you’re welcome.

 

Beth Probert:

And Dr. LeBlanc, we have a question from Shannon from Boston, and her questions is, “How can I manage the daily stress of like with AML? Are there proven strategies to cope with the stress?” So, we did talk about a few things earlier, but what advice would you give Shannon?

 

Dr. LeBlanc:

Yeah, I’m not aware of proven strategies specifically for AML, which is part of where we all struggle. Not knowing what to do and how to best support individual patients. And as I mentioned earlier, every individual is quite different. but I usually recommend meeting with a professional to talk about it. And some people are opposed to that and they don’t want to do that, but more people are at least open to the idea. And so, Shannon, if you’re somebody who’s open to that idea, I would actually encourage you to seek out a specialist in palliative medicine.

And many people misunderstand what that means. So, I want to just take a moment to explain why I would think that’d be helpful and what the evidence shows. So, clinicians who are trained in palliative medicine are basically experts on well-being. 

They know how to address symptoms, they know how to help with quality of life maintenance, and they know how to help people cope with difficult diagnoses and serious illnesses like cancers. Regardless of the expected outcome. So, they can be helpful if we’re aiming at cure and we think there’s a really good chance of that, and they can be helpful in cases where we know that’s not gonna happen, and anywhere in between.

So, one of the misconceptions is that they can only be helpful when people are dying, but actually, what we found in a lot of research is that when you add a palliative care specialist to the cancer care team, even from the point of diagnosis, that patients feel better, and they do better, and even live longer. Several studies, now, have shown that in a recent medi-analysis that we publish, for example.

So, part of the mechanism by which palliative care specialists help patients feel better and live better is not only by addressing physical symptoms, but also at addressing these difficult emotional and existential kinds of issues.

Helping with coping. How do I get through the day; how do I live with the fear that this diagnosis instills in me; how do I enjoy life? Those kinds of questions are very common. And palliative care specialists are often very equipped at helping. Or even psychologists would be another great resource, where this is a person you’re going to see where the entire focus of the visit on those issues, so that they definitely don’t get pushed to the last 30 seconds of the visit when the doctor has their hand on the door knob and they’re trying to get out to the next patient.

 

Beth Probert:

Wow, and I love what you said that your study shows that people who do seek out the palliative care will live longer. And seeing a counsellor or psychologist too, both of those are just amazing suggestions. Thank you.

We have one last question from Doug from Boise, and, Michelle, I’m going to direct this question to you.

Doug says, he doesn’t know how to find a support group. So, where does he start? Could you give us some feedback?

 

Michelle Rajotte:

Sure. He can start by calling us. We can try to find out if there’s one locally for him. There’s also access to the online chat, which meets in the evening and he can talk with people that way. There’s a lot of different options. So, there’s the traditional support groups that you go to, but there’s other ways of getting support, as well. So, that’s a good way to start. It can be very overwhelming to try to find one. The other thing you can do is if you’re being treated at a hospital, talk with the hospital social worker because they’re usually pretty knowledgeable about what supports are in the area. But I would say those would be the two good places to start.

 

Beth Probert:

That’s wonderful. And Michelle, can you give us your specific phone number and email where people can reach you and your department?

 

Michelle Rajotte:

Sure. So, the number to the Information Resource Center, we’re available Monday through Friday, 9:00 a.m. to 9:00 p.m. is 1-800-955-4572. The other way to access us is through the website, which is LLS, short for Leukemia Lymphoma Society, much easier to type, .org. When you get on there, there’s a way to reach the information resource center either by email, by chat, or the phone number will be there, as well, if you need it. But that’s really the best way to reach us.

 

Beth Probert:

That’s wonderful. And we just got one last question, and we have enough time for it. And Jim, I’m wondering if you have some advice about this question. And it is, “My partner’s often struggling deeply with the diagnosis. I don’t know the right words to say to help him feel better.” Could you give some advice to this topic, Jim?

 

James Bond:

Yes. The weekend I was diagnosed, the very qualified oncologist rightly said in response to my question, “How long do you think I’ll live?” He said, “At most you’ll live three years.” And so, I struggled, my wife struggled, I was in my early 40’s, that weekend was hell. And here’s what got me out of my funk and got us back to problem solving and putting this thing on our agenda to do all we can. I looked back at my own life, here I am in my 40’s, two boys, I’ve been healthy most all my life. And I thought of, there was a real setback, medically I had, a bad injury playing sports when I was in high school, and to me as a high school kid, that was the end of my life. Sport was gone; a lot of recuperation.

 And as I looked back on that with this cancer diagnosis, I said, “You know what, as tough as that was at the time, as devastating as that was, a lot of good things happened because of that setback.” Real things. Like it got me studying a lot more in college, I got a nice job as a result of it. Lots of good things happened. It caused me to overcome things, and I said to myself and my wife, “Hey, we’re gonna make this deadly cancer diagnosis the same thing.” And like all of us I think have been saying: every case is unique.

So, I don’t get bummed out when people give me their prognosis or whatever, or I read something that’s not good. My case is different than everybody else, and we can look at it that way. And in the end, this can happen to any of us. So, it got me off my back, it got us in there fighting, and that’s the way I look at it.

 

 

Beth Probert:

That is wonderful advice, and what I hear you saying is that, really, with your care partner, and your family, and I’ve heard this from Dr. LeBlanc and Michelle, as well, and, of course, Jim, that you’re a team. And finding that way to survive this as a team, so that’s great advice, Jim. Thank you.

 

James Bond:

You’re welcome.

 

Beth Probert:

So, I do want to thank the Patient Empowerment Network for this really impactful program today. I’d also like to thank The Leukemia and Lymphoma Society for partnering with us on this webinar. And I would like to thank our guests as we come to a close to this program. So, Dr. Thomas LeBlanc from the Duke caner institute, thank you so much for taking the time today and sharing the real benefits of the focus on the palliative care.

And Michelle Rajotte, from The Leukemia and Lymphoma Society. Your contribution has been wonderful, the resources that your department does provide. And Jim Bond, it’s just been so great hearing from you and your very long journey with AML, and what you’re dealing with, and how you have made the best life possible, and all of your dedication to advocacy. So, thank you so much for joining us today.

 

James Bond:

You’re Welcome.

 

Beth Probert:

And if our viewers have missed anything or just want to re-watch the webinar, a replay will be available in the coming weeks. Thank you for joining us, I’m Beth Probert, and I look forward with meeting with the AML community again. Thank you.


We thank Celgene Corporation, Daiichi Sankyo, Genentech, Helsinn, and Novartis for their support.

ASH 2018 – Exciting News in CLL Treatment

CLL patient advocate, Lee Swanson, interviews Dr. Adrian Wiestner, Senior Investigator, Laboratory of Lymphoid Malignancies National Heart, Lung, and Blood Institute (NHLBI), National Institute of Health (NIH), about the exciting news in treatment of CLL.


Transcript:

Lee Swanson:

Hello.  I’m Lee Swanson, and this is the American Society of Hematology conference in a chilly San Diego today, at least by San Diego standards.  And we are here today just outside one of the meeting rooms where a lot of people, clinicians and researchers are finding out about new developments.  And joining me is Dr. Adrian Wiestner from the National Institutes of Health, the Heart, Blood and—Heart, Lung and Blood Institute.

And what are the exciting things to you about the research developments in CLL at this conference?

Dr. Wiestner:
So what’s most exciting really is the development of novel therapies for patients, and that’s—you can only say it’s starting to be old news, because ibrutinib (Imbruvica) has been approved two years ago, but we’re still learning about how well this treatment actually works for people and how it can start to replace chemotherapy probably for most everybody with CLL.

And then there is exciting developments in regards to other treatments, venetoclax (Venclexta), some of the newer kinase inhibitors, so a lot of treatment choices being really worked out for patients.

Lee Swanson:
And those are drugs we know about, the ones that you’ve mentioned.  There are a lot of things in the pipeline as well, aren’t there?

Dr. Wiestner:
There are things in the pipeline, but I think we actually have the tools or the color, if you wish, and now it’s about really painting the path forward in the sense that how do we best integrate these different tools into one strategy.  And there’s research on what strategy is maybe best fitted for some genetic profiles in CLL versus others. So if you have a very benign genetic profile in CLL, maybe just ibrutinib alone or a kinase inhibitor alone will work.

We’re learning that other patients will need combination therapy.  We’re seeing that combinations can be done safely.  We’re learning that combinations can improve efficacy.  An example is the combination of these chimeric antigen receptor T cells, the CAR‑T cells, is highly effective and patient‑derived cells that can attack CLL.  So that becomes more efficacious and actually also better tolerated when you combine it with ibrutinib.  I think that’s—this is an example of how we’re still learning how to put the things together.

Lee Swanson:
So from a patient’s perspective how should they find out about clinical trials or new developments like this?  What’s their best path?

Dr. Wiestner:
So there are many good places to learn about this.  Patient Power is one of them.  There are other patient organizations that can be found on the ‘net.  There’s The Leukemia & Lymphoma Society that has information.  Then there is the NIH has several resources for patients.  So you can Google “clinical center CLL.” You can Google “NIH” in general.  There is a website that’s called clinical trials where people can search with a disease, with a diagnosis, with a location, even with a treatment.  So it’s very customizable to search for clinical trials in your area.

Lee Swanson:
And then, of course, they have to figure out, work with their doctor to fill out if that’s a fit for them.

Dr. Wiestner:
Right.  Obviously, yes, for all clinical trials.  Yes.  Yes.  That’s—but a lot of the really exciting developments are transitioning into also clinical care.  There are big clinical trials set up by cooperative groups across the country, so there are—will be opportunities to really participate.  And I think it’s—it is key to keep participating in the trials.  We have the tools, but again how to best put them together can only be found out by clinical trials.

Lee Swanson:
Okay.  Well, thank you very much.  Appreciate you being here with us today.

Dr. Wiestner:
Thank you.

Lee Swanson:
And I’m Lee Swanson at the American Society of Hematology conference.  American Society of Hematology.

On the Horizon for Multiple Myeloma

ASH 2018 Conference Coverage

Dr. Elisabet Manasanch, Assistant Professor Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, shares what’s the latest and on the horizon for Multiple Myeloma.

ASH 2018 – Multiple Myeloma Highlights

A Multitude of Options in Myeloma

Dr. Robert Orlowski, Director of Myeloma and Professor in the Departments of Lymphoma/Myeloma and Experimental Therapeutics at The University of Texas MD Anderson discusses the multiple myeloma highlights and what patients can be excited about from the ASH 2018 meeting.


Transcript:

Esther Schorr: Hi there. This is Esther Schorr from Patient Power coming to you from ASH 2018 in San Diego, and I have with me today Dr. Bob Orlowski who has joined us at Patient Power before. He’s the Director of Myeloma and Professor in the Departments of Lymphoma and Myeloma and Experimental Therapeutics—that’s a very long title—at the University of MD Anderson—University of Texas MD Anderson. Sorry.

Dr. Orlowski: Thanks very much for having me.

Esther Schorr: I’m glad you’re here again.

Dr. Orlowski: It’s a pleasure to be back on Patient Power.

Esther Schorr: Thank you, sir. So what’s going on in myeloma now at ASH? What are the highlights? What are patients going to be excited about, and what are you excited about?

Dr. Orlowski: One of the exciting areas is definitely talking about the different therapies that are targeting what’s called BCMA or B-cell maturation antigen. This is a protein on the surface of myeloma cells, and the excitement about it is it’s a target which is almost only on myeloma or normal plasma cells, not on other kinds of tissues. And that’s important because if you want to target for immunotherapy, you don’t want that target to be on too many normal cells, or the immune therapy will kill those cells and cause side effects.

So there are really three categories of drugs now that are looking very attractive. One is what’s called an antibody-drug conjugate. So this is a plain old antibody that has another chemical attached to it, and it’s given usually IV right now, attaches to the myeloma cell. It then gets inside the cell and the drug is released. So the antibody is essentially like a carrier molecule.

Esther Schorr: Kind of like a cruise missile?

Dr. Orlowski: Sort of like that. I like that analogy, yes. And then it blows up, using that analogy, the cancer cell once it’s inside.

So one of the first of these drugs that already is in the clinic is showing a 60 percent response rate in very heavily pretreated patients. The registration study, meaning the trial that hopefully will get it approved by the FDA, has already finished enrolling, so we’re hopeful that maybe by the end of 2019 this drug as a single agent will be available. And it’s really easy to give. It’s IV once every three weeks, which is pretty darn good.

Esther Schorr: And what’s the drug called? I’m sorry I missed that.

Dr. Orlowski: Well, it’s a good question. Actually, it doesn’t have a name yet, which is why I didn’t tell you what it’s called, but the abbreviation for it is GSK 916.

Esther Schorr: Okay.

Dr. Orlowski: And the reason for that is it’s actually quite expensive to come up with a name, because they have to find a name that, first of all, is not confused with other drugs so that it minimizing errors and also one that us poor feeble-minded doctors will remember so that we prescribe it often.

Esther Schorr: We’re not sure how you can remember all the letters anyway. Okay. So that’s one. Is there something else going on that you got to share?

Dr. Orlowski: So a second category of drugs that target the same protein, BCMA, the first formal presentation of those data were shown here at ASH, and this is what’s called BiTE or Bi-specific T-cell engager. And it’s sort of is a molecule, if you want to use the cruise missile analogy, that has two war heads. One end binds to the cancer cell. The other end binds to the patient’s own T cell, brings them together and the T-cell attacks the cancer cell. So it’s a way to use immune therapy with the patient’s own immune cells, and there are reports here of the first one of these which is called AMG 420. Again, doesn’t have a name yet, but it’s showing in very heavily pretreated patients complete responses with MRD, or minimal residual disease, negativity, which is really exciting.

Esther Schorr: So and that’s different than—and we’ll probably talk about it in a minute—that’s different than CAR-T.

Dr. Orlowski: Exactly.

Esther Schorr: Okay. So we can talk about that in a minute.

Dr. Orlowski: Yeah, that would be great. So the next topic is the CAR-T, also against B-cell maturation antigen, or BCMA. It’s a little more complicated though because what you have to do is you take out the patient’s own T cells and then in a laboratory you infect them with a virus. The virus has a gene in it that expresses a receptor on the T cells so that they can better recognize the cancer cells.

Esther Schorr: An invitation.

Dr. Orlowski: Exactly. Kind of. I like that.

Esther Schorr: Okay.

Dr. Orlowski: And then you infuse the cells back into the patient. They find the cancer cell, they attack it, and they kill it. So it’s great, because it’s personalized. It uses the patient’s own T cells. The problem is that it takes two to four weeks to manufacture the cells after they’ve been taken out of the patients, and so in the meantime the myeloma can sometimes be creeping up. So that’s one problem.

And also there are activities with the disease or with the T cell against myeloma, but there are also some side effects like cytokine release syndrome. But the response rates with some of the more advanced molecules are in the 90 to 100 percent range, and the durability of that is at least a year to 18 months, depending on what patient population you look at. And those are the most mature data of the three categories of immune therapies that we’ve talked about.

Esther Schorr: So of those three are any of them being looked at for first-line therapy, or these are at the moment still for people who have relapsed or are more difficult cases?

Dr. Orlowski: Right now it’s more for very advanced disease, but there are already trials planned with all three of these technologists in earlier patients and some in newly diagnosed patients, especially those with high-risk disease, because they still don’t do as well with standard therapies that we have. So it’s really an exciting time because these are some of the best results we’ve had in very difficult to treat patients, which means they should work even better when we give them earlier.

Esther Schorr: So one other question then. What’s happened to stem cell transplants for multiple myeloma patients? With all of these new combinations of treatment s, where is that in the mix of consideration for treatment?

Dr. Orlowski: Stem cell transplant is still considered part of the standard of care for patients with newly diagnosed myeloma, and in some cases it can be used for relapsed disease, especially if the patient had a really good durable benefit with a first transplant. The advantage of the stem cell transplant right now is that it with works very well, the toxicity profile is very well defined, and compared to a CAR-T cell it’s actually relatively cheap. But as the technology hopefully becomes cheaper and more available there would be great interest in comparing outcomes of people getting chemo plus a transplant, for example, versus chemo plus a CAR-T cell.

Esther Schorr: So it sounds like there’s a lot more options that are coming up for multiple myeloma patients. Is there anything else that patients that are listening would want to know about, that they should feel good about?

Dr. Orlowski: Well, there’s a lot more data with other immune therapies including earlier use of daratumumab (Darzalex), which is an anti-CD38 antibody. One of the presentations, which is still to come on Tuesday, shows the data of that drug with lenalidomide and dexamethasone in previously untreated patients, and the results really look excellent. So that will probably be one of the new standards of care for transplant ineligible patients. And there are studies ongoing with daratumumab in transplant eligible patients as well.

Esther Schorr: That’s a lot.

Dr. Orlowski: And that’s not all of it, but I think that may be all we have time for.

Esther Schorr: Thank you so much, Dr. Orlowski, for being with us again and making this a little more comprehensible for us normal mortals.

Dr. Orlowski: Thank you very much.

Esther Schorr: This is Esther Schorr coming to you from ASH. And remember, knowledge can be the best medicine of all.


Please remember the opinions expressed on Patient Empowerment Network (PEN) are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

ASH 2018 – Latest News and Research in CLL

CLL patient advocate, Lee Swanson, interviews Dr. Kerry Rogers, Assistant Professor, Department of Hematology The Ohio State University Medical Center, about exciting CLL news and research from the ASH 2018 Conference.


Transcript:

Lee Swanson:

Hello.  I’m Lee Swanson, and this is the American Society of Hematology conference in San Diego, and I’m happy to be joined today by Dr. Kerry Rogers from the Ohio State University Medical Center.  And you are a CLL specialist.  What at this conference has excited you that patients should know about?

Dr. Rogers:

I think there’s a couple really exciting things at this conference that will be very important for patients.  Probably the most exciting thing, in my opinion, hasn’t been presented yet but is being presented later today by one of my colleagues.  And then there’s a late‑breaking abstract that will be Tuesday that’s really exciting.

And these are studies comparing ibrutinib‑based regimens to a chemoimmunotherapy regimen.  So that’s a comparison of a pill targeted agent with a course of chemotherapy with an antibody, and the exciting thing here is that taking the pill oral targeted agent seems to be doing better for patients in a really important way which is how long people are living without their CLL progressing or returning.

So this is the first time we’ve had a large‑scale comparison of a chemotherapy to a chemotherapy‑free treatment.  And just to go into a little bit more detail, if that’s okay, there is a study through a cooperative group called the Alliance, and that is a group that does very large studies at multiple centers in the United States that compared BR to ibrutinib to ibrutinib and rituximab.  They found that there is no difference in something called progress‑free survival, which is how long people are alive without their CLL returning or causing problems between both the ibrutinib arms, but a substantial improvement between the ibrutinib treatment and the chemotherapy treatment, which is bendamustine and rituximab.

So this means that ibrutinib regimens are out performing chemoimmunotherapy, and that was in people 65 and older.  And I think that’s very exciting because it’s showing that we can treat CLL more effectively in this way than with BR which is the standard chemoimmunotherapy, and these are all people who are taking their very first treatment for CLL.

There’s a similar study in younger patients comparing FCR to an ibrutinib‑based regimen with very similar results.

Lee Swanson:

Really.  So are we looking at a day when that will become standard of care?

Dr. Rogers:

I firmly believe that‑‑of course, each individual person needs to select a treatment that’s best for them, but I think it is a standard of care now to do an ibrutinib‑based treatment rather than chemoimmunotherapy for the majority of people taking a first treatment.

Now, there are select individual patients who will have a very prolonged benefit from FCR, people who have an IGHV mutated status, so it’s a particular test that shows that these people have just a very nice benefit from FCR, but other than that group it is now the standard to do these ibrutinib‑based treatments.  And I think both these studies are what is showing us that this is a standard.  It’s definitely the most important thing for CLL I think at this meeting.

Just to plug how important this is, my colleague, Dr. (?) Wyak, who’s presenting the Alliance study, is doing so at the plenary session, and that’s the talk where they pick the very, very best kind of studies or data from the entire meeting, so not just CLL but noncancer blood disorders, other blood cancers.  So this is really a very important thing for people with CLL.

Lee Swanson:

Show how does a patient go about talking to their doctor about these emerging…

Dr. Rogers:

Yeah, so I think it’s really important to be able to ask your doctor anything, and this is something that people should talk with their doctor about.  Both these studies were in people taking a first treatment for CLL, but that doesn’t mean that this type of finding isn’t important to other people.  And I think if you’re considering a first treatment for CLL and need a first treatment for CLL I think sitting down with your doctor saying, you know, finding out what they recommend but then also saying, you know, how do you feel about these chemotherapy treatments versus ibrutinib‑type treatments and seeing what they have to say.

And of course I think it’s very fair since this data is going to be presented at this meeting to ask your doctor about these large studies.  These are the type of really big studies that should be understood by the majority of oncologists.  So I think it’s okay to ask them specifically, just, hey, what do you think about the studies comparing chemotherapy to ibrutinib?  How does that apply to me as a person?

Lee Swanson:

So chemotherapy of course is a refined, six sessions or generally.  Ibrutinib, are they then looking at a prolonged use of ibrutinib?

Dr. Rogers:

Yes.  So both these studies, the ibrutinib was continued indefinitely which is the way it’s supposed to be prescribed in the United States, versus chemotherapy, which is a combination of chemotherapy and then antibody for about six months of treatment, so that is an important consideration.

Also at this meeting there’s data about combination regimens that don’t include chemotherapy that are a fixed or limited treatment course, so I think that’s also very exciting.  Those studies are now not very far into follow‑up, so people have only finished those treatments for a year or so.  I think that when we look at these chemotherapy‑free combination treatments we’re really going to need to see how long people do really well after they finished treatment to know what the true benefit is, but that’s also very exciting to see that happening.  It might allow people to avoid chemotherapy, stop treatments and get very good remissions that last years and years.  We just haven’t had them long enough to know the years and years yet like with some of the chemotherapies.

Lee Swanson:

Of course.  So one of the‑‑one of the things about CLL is that it finds a way around treatment often.  They clone cells or what‑have‑you that then, you know, so you’re looking then at second‑ or third‑generation medications sometimes.

Dr. Rogers:

Yes, that’s true.

Lee Swanson:

So that’s going to be a continuing challenge.

Dr. Rogers:

Yes.  I think that is a continuing challenge, and when we see more of these people taking these oral targeted agents, these pill treatments that aren’t chemotherapy that are taken for an extended period of time we’re going to see more people where those treatments stop working or develop resistance, and just because we’ve now shown it’s superior to chemotherapy‑based treatments as a first line doesn’t mean that these are perfect.  So we are still working very hard on what to do after you take something like an oral targeted agent for first treatment or even a second treatment or a third treatment.  There’s a lot of research at this meeting being presented in that area too.

We’ve shown venetoclax works well after ibrutinib, but we still are trying to get a handle on has works well after venetoclax.  There’s some kind of laboratory‑based data around venetoclax resistance being shown at this meeting, and I think that’s going to be important too because that’s what helps us build better treatments for those people is to really take a deep look at what’s happening on a cellular level in the leukemia.

The thing I actually saw this morning that I thought was very exciting for people who might have developed resistance to one or more targeted agents is actually CAR‑T therapy.  I think that the more I’ve seen data coming out with that the better it’s getting, the better we are getting at giving that to people.  And while that is definitely not therapy right now for the majority of CLL patients there are definitely some people that benefit from that type of treatment that have participated in research studies with it.  And I think that’s something that’s going to advance and fill some of the need for what we’re going to ideally offer people who have had their CLL come back on these targeted therapies.

Lee Swanson:

So CAR‑T, it’s worked very well for some people.  It’s worked not at all for other people.  Is there a way to be able to target who’s who?

Dr. Rogers:

You know, I really hope so.  Right now I don’t know that we’ve come up with a firm to target who’s going to benefit the most and who’s not going to benefit, but I do think the more experience we get with that the more we’re going to learn about not only who will benefit but also how to make it so more people benefit.  So going in, instead of saying X many people benefit, have a higher percentage of people that undertake it do well with it and to have the side effects of it reduced.  You know, that’s not a fun and easy treatment, so I think the continued work to reduce the side effects and also get it to work for more people is going to be really important.

Lee Swanson:

Well, thank you very much for your time.  We really appreciate it, and it’s very good to talk to you.  Thank you.

Dr. Rogers:

You’re very welcome.

Lee Swanson:

I’m Lee Swanson at the ASH conference in San Diego.

ASH 2018 AML Roundtable

Latest Research in AML


AML experts Dr. Sangmin Lee, Assistant Professor Weill Cornell Medicine, Dr. Ellen K. Ritchie, Associate Professor of Clinical Medicine Weill Cornell Medicine, and Dr. Tapan M. Kadia, Associate Professor Department of Leukemia The University of Texas MD Anderson Cancer Center, join this roundtable to discuss all the new drugs to treat AML.


Transcript:

Andrew:

Hello. I’m Andrew Schorr from Patient Power. Welcome to our program, from San Diego and the American Society of Hematology meeting, where the people from around the world discussing the latest in blood related conditions. And there is a lot of discussion given new drug approvals and lots of research in acute myeloid leukemia. And it gives new hope to patients and their families dealing with this acute condition. So, joining me is Esther Schorr. And Esther, you’ve been talking to people. And we have a wonderful panel we’re going to meet, in a second.

 

Esther:

I have. And, especially with the more acute conditions that these wonderful researchers and clinicians are working with, I think that we need to discuss how family members, care partners, caregivers, what active role they need to play in sort of the rapid fire beginning of getting treatment.

 

Andrew:

How you want the best yourself for a loved one. Let’s meet our panel. So, I’m going to have you introduce yourself, so we get your titles right and your institution, please. 

Go right ahead.

 

Dr. Lee:

So, I’m Sangmin Lee from Weill Cornell Medicine. And I’m part of the leukemia program. And I’m an assistant professor there. And I focus on myelodysplastic syndrome and acute myeloid leukemia.

 

Andrew:

Okay. And next to you is a colleague of yours.

 

Dr. Ritchie:

My name is Ellen Ritchie. I’m an associate professor of clinical medicine and the assistant director of the leukemia program at Weill Cornell Medical College. I treat all myeloid malignancies. And I also treat acute lymphoblastic leukemia.

 

Andrew:

Okay. And both, two New Yorkers. And now, let’s go to Texas.

 

Dr. Kadia:

I’m a Texan but a former New Yorker. My name is Tapan Kadia. I’m currently associate professor in the Department of Leukemia at MD Anderson Cancer Center in Houston Texas. My practice is based on research and clinical work in acute myeloid leukemia, MDS. I also look at bone marrow failure syndromes. And I’m glad to be here, so thank you.

 

Dr. Ritchie:

Thank you for having us.

 

Andrew:

So, Dr. Ritchie, I’m going to start with you for a second. So, are we right? It seems like someone’s head can spin, with all of the new drug approvals, and then, also trying to make sense of what’s right for what patient. So, how much have things changed in AML?

 

Dr. Ritchie:

Well, AML used to be a really simple disease because we had two drugs, and that’s how we treated patients. Now, it’s a more complicated disease, partially, because we’re learning a lot more about this disease molecularly. And there are new targeted agents, which have been recently approved, in the last year, for the treatment of AML. Many of them, just recently, in the past few days. Gilteritinib, which is a second FLT3 inhibitor was in there last week. A lot of these drugs are drugs that fall into two categories. Some which target mutations that may be relatively infrequent like IDH1, IDH2, FLT3.

And these are for those specific populations who have those particular mutations.

There are also drugs that are more blanket that cover patients who have really any abnormality, which are added to standard therapy like Venetoclax. Venetoclax was initially approved for the treatment of CLL and has recently had a new label to add to low dose ARA-C or to hypomethylating agents, for the treatment of AML. And that’s an exciting new development where the response rate with hypomethylating agents goes from about 40% to 70%. So, it’s a real advance, for those particular patients.

Also, in the really older and frail population, I always have problems saying it, Glasdegib, which is really a drug, which is directed at the leukemic stem cell together with low dose ARA-C. These have been approved really for patients who are a little bit more frail and older. And it’s a regimen that is more easily tolerated by that age group.

 

Andrew:

So, just a follow up. So, how much of a difference – the FDA approves effective therapies effective therapies, which, hopefully, make people’s life better and longer. So, is that the hope for our viewers watching that whether it’s themselves or an adult parent or grandparents that they can have a better, longer life?

 

Dr. Ritchie:

Well, there are a lot of aspects to leukemic care. It’s not only having a longer life but having a higher quality of life. So, it’s the quality of life that you have, as well as the length of life that you have. So, just to put it in reference, standard induction chemotherapy, where we use two drugs, Daunorubicin and Cytarabine, which my father used to use when he practiced medicine, and those days are – it’s an old combination. But it really requires the patient be in the hospital for 30 days. And these patients are sick. And they require transfusions.

And most of them require antibiotics. And they don’t feel very well, and it’s a difficult time. So, for older patients, are you really willing to spend a month of your life or maybe two months of your life where you really feel terrible in the hospital? That’s not necessarily something that you want to do. So, part of the breakthrough is not just that we may improve overall survival, which we don’t really know, until it’s out in the community, and we see how it works. But whether we can improve the overall quality of life of older patients who have AML. So, and rather than being in hospital, you can have your therapy, in an outpatient setting.

And rather than it being all intravenous, you might have an oral medical that you could take at home, like you do your hypertension pill, really, for your AML. So, these are really important advances because it enhances the quality of life of patients who have acute leukemia.

 

Esther:

Well, and it also sounds like you referenced that a lot of the patients are older with this. And I just can’t imagine what it must be like, if you have two much older people, and one person is, as you mentioned when we were talking earlier, one is out of commission.

The other is not only going to need support from family, but if their partner doesn’t have to be in the hospital to be able to at least be home, there’s some level of support there.

 

Dr. Ritchie:

Right. Well, you guys can chime in. But a typical situation, really, is two older people who are living together where they’re doing just fine as a symbiotic couple. But they both have their illnesses or both have their problems. But once you take one person out of the picture, and that person is very, very sick, it can be very difficult for the other elderly person to actually handle all of the stress of taking care of themselves and all of the stress of taking care of another person. So, one of the key factors, I think, in overall survival and quality of life in patients who are older who have AML is having a caretaker who is reliable for them.

And that may be your child. It may be your sister. It may be a good friend. But there has to be someone in your life, beyond just your spouse, who can be a caretaker for you for a successful therapeutic result.

 

Dr. Lee:

And one thing that is great about the medicines that are coming out are that they’re very well tolerated, especially the IDH drugs and Venetoclax. They’re very well tolerated. You can do it outpatient. So, for a lot of older patients, as you know, if you stay in the hospital more, you’re exposed to infections. Your performance status may decline. So, patients actually do better with an outpatient therapy. I think that’s beneficial

 

Esther:

And also older people. I have two aging parents, thank goodness doing well. But they’re in their 80s. And just driving to the clinic is a big event. But if you’re having to do that every day for treatment or going to visit.

 

Dr. Ritchie:

Right. And we don’t want sick people driving necessarily to our clinic because, if your hemoglobin is 7, and your platelets are low, you’re not in the best situation to be reactive to the problems of traffic and cars.

So, transportation is also a real issue, I think, when patients are older and coming in for treatment.

 

Andrew:

Dr. Kadia, so we’ve mentioned a couple of these cancer genes. IDH, FLT3, I think. So, these are oncogenes, right?

 

Dr. Kadia:

Right. So, what’s been great, and I think this has been greatly summarized by my colleagues, but we’ve had sort of a revolution in how we treat AML and many cancers, but particularly AML and the liquid tumors. With the advent of what we call next generation sequencing, we’re able to really get the mutations and the data from the leukemia cells. We find that there are recurrent mutations. Mutations are changes in the DNA that happen over and over and over again, in different people with leukemia. So, it made us realize that, if these mutations keep happening in AML, they must drive the AML.

There must be something about them that makes the AML happen. And, in fact, that’s the case. So, in a handful of those mutations, things that people have really studied, we now know that things like FLT3 or “flit 3” is a mutation that really drives proliferative AML. And so, people said, well, if that drives it, can we develop a drug target inhibitor of that mutation to shut the leukemia down? And indeed we can. We used to use a drug call Sorafenib last year, over a year ago. A drug called Midostaurin was approved with chemotherapy in the front line. And just recently, as was describe, just a week ago, Gilteritinib was approved in patients who have the FLT3 mutation, but they’ve had relapsed disease.

So, that’s just one example. The second you said IDH, right, isocitrate dehydrogenase, another mutation. We didn’t know what it meant. But people worked and worked and figured it out. And they found out there’s two mutations, an IDH1 and an IDH2 mutation. Each of those drives that particular subset of leukemia. And it turns out you can make inhibitors to each of those, and they work. An oral medication you take once a day for people with relapsed disease actually works.

And it doesn’t work like regular chemotherapy. We describe intensive chemotherapy. You put them in the hospital, their hair falls out. They have mouth sores and diarrhea and nausea and vomiting. We don’t see that, with these pills. We do see some side effects. And, certainly, the patient and the family member need to recognize those side effects. So, there are side effects. But they’re different. They’re more tolerable. They’re more manageable. And so, that’s what we’ve been able to do, get people home, take these medications, and target these specific mutations.

So, among the many mutations we’ve discovered, we found drugs for probably two to three of those targets. But we also found that some of these mutations will predict for responses to other drugs like Venetoclax.

 

Andrew:

Let’s talk about testing. How do you know?

 

Esther:

I was just going to say it really sounds like you have to be tested.

 

Dr. Lee:

Yes.

 

Esther:

To know where you fall.

 

Dr. Ritchie:

And I think that’s one of the big barriers right now that I feel the insurance industry has not really caught up to what it is that we’re doing in AML. So, every patient who is getting or has a suspicion that patient has AML, that patient, when they have a bone marrow biopsy and they see a doctor should have a next generation sequencing sent.

The problem is this costs thousands of dollars. Now, some insurance companies are not – they don’t really care or aren’t really cognizant of the quality of the different NGS panels. And they make deals to cover with one or not cover at all. So, it can be a hassle for the patient. And it can be thousands of dollars expense. So, that’s something that I think the whole industry is working on to try and enlighten insurance companies and to make them pay for this particular sequencing. MD Anderson has their own in house. And you probably have worked out a deal with insurance companies.

 

Dr. Kadia:

No, we have. So, I think more and more, insurance companies are beginning to realize that this is a part of the disease treatment. If you have pneumonia, you’re going to get a chest x-ray. If you have AML, it’s becoming standard.

It has for years. We do FLT3 mutations. We do something called NPM1 mutations. For years, we’ve been doing this in AML. Now, what they need to realize is that we need to expand that to what we call a sequencing panel, which are 80 different genes, which are commonly mutated. Why? Not just because we’re interested and we’re curious, but because these mutations play an important role in telling the patient this is your prognosis. And this is the drug that we’re going to treat it with.

 

Dr. Ritchie:

Or even, if this patient – and just because you’re older doesn’t mean you’re not a candidate to be a bone marrow transplant candidate, there are some mutations that we find that really propel us to wanting to have that patient –

 

Andrew:

It’s all about getting what’s right for you or your loved one. So, let’s back up for a second, Dr. Lee, just so we understand AML. So, first of all, how old is the typical patient? What are the symptoms that present? For somebody who is watching us, maybe somebody said this could be AML.

 So, what is AML? And how does it typically show up and for who?

 

Dr. Lee:

So, AML stands for acute myeloid leukemia. So, in your bone marrow, bone marrow’s job is to make blood cells, including your white blood cell, which is your immune system, hemoglobin, which are the red cells, and platelets. And they all are manufactured in the bone marrow. So, what we’re talking about here is that, basically, the factory, the stem cells that make the blood cells, have gone wrong, basically. And there are abnormal myeloid stem cells that proliferate. And your bone marrow is full of these abnormal stem cells that are not able to make normal kinds of immune system and hemoglobin and platelets.

So, it’s an acute leukemia meaning that, sometimes, people are doing – a lot of times, people are doing well. And then, all of a sudden, their bone marrow develops a leukemia. And all of a sudden, you become symptomatic.

So, symptomatic means that, if your bone marrow is not making red cells or platelets, you might be more tired. You might see some easy bruising or see these little dots pop up on your skin.

 

Andrew:

Petechiae.

 

Dr. Lee:

Petechiae in your skin. Or you might have an infection that doesn’t go away because your immune system is affected. So, there are various ways that people are diagnosed, based on how they feel. Sometimes, people just get a routine blood work by the primary physician, and they are just discovered to have leukemia, even though they don’t have symptoms. So, it kind of varies.

 

Esther:

But there’s different paths with leukemia, obviously, that there’s AML, which is do not pass go, something needs to happen right now. And some of the more chronic forms where you have a little more time to kind of figure out what’s going on.

 

Dr. Lee:

And a lot of times, you can differentiate because, if you see a primary care physician or Emergency Room, they can actually look at the blood cells and do what’s called a manual differential.

Basically, some person looks at the blood cells under a microscope, and you are able to see abnormal leukemic looking cells that you wouldn’t see in any other condition. So, that’s how you know that you have leukemia.

 

Andrew:

So, a family is saying, okay, did we do something, did the patient do something, did something happen to them that caused this. So, you sort of fall off of this leukemia cliff into this acute I call five alarm fire situation.

 

Dr. Kadia:

No, you’re absolutely right. And I completely agree with that. Leukemia, at least AML, acute leukemia, is a very rapidly progressing disease, in most cases. And it’s, usually, a medical urgency, if not a medical emergency, like you said. Most of the time, no one has done anything to cause leukemia. And many people are doing fine, until they actually have the diagnosis, and they get very, very sick very rapidly. Patients tell me all of the time, I was just traveling. I was on a cruise. I was playing golf. I felt fine. Why do I have AML? It comes on very acutely, hence the name acute, so very quickly.

The risk factors for AML, first, is age. The older you are, the higher the risk of developing AML. The average of developing AML is around 68 years of age. We know that there are younger people who get AML as well. But we know that that AML is a little bit different than people who have older AML. The younger AML’s tend to be more rapidly proliferative. They have high white counts. The older AML is often associated with a disease called myelodysplastic syndrome, which is related. So, they have low counts, feeling kind of icky. Their counts are not great. And then, they develop this surge.

And so, age is certainly a risk factor. Prior exposure to chemotherapy or radiation for another cancer predisposes you to AML. If you are exposed to things like benzine or if you’re a heavy smoker that can sometimes predispose people to AML. But, certainly, it’s not anyone’s fault. And no one knows. And why couldn’t I have detected this earlier? Nine times out of ten, you could not have detected it earlier. It happened two weeks, three weeks prior to what just happened.

 

Esther:

And is the treatment for a younger patient different than for an older patient?

 

Dr. Kadia:

It can be. It can be. And often, what we look at, and age is not the only thing. We don’t look at age as a number but more of a fit and unfit person. So, if an older patient, they tend to have more comorbidities, history of hypertension, diabetes, heart disease just because they’ve lived longer. They have 60, 70-year-old organs. And they may not be as fit as a 25, 30, 40-year-old. And so, then, you base your treatment paradigm on whether you think they can tolerate some intensive chemotherapy versus not.

But a point that I wanted to expand on, when you present in the Emergency Room with acute leukemia, it’s a rare folks, 19,000 cases a year, compared to something like breast cancer or lung cancer, which is very, very common. And so, typically, someone will come to the Emergency Room. They’ll be seen by the Emergency Room. They’ll consult the local hematologist oncologist. They’ll come to see that patient. Or they may know a local hematologist oncologist.

While community physicians can treat the disease, sometimes, in the acute setting, and for reasons we described earlier, it’s nice to go to an academic center or larger center who can do some of the initial work up, the mutation screening, it will be easier.

Maybe not have problems with getting the insurance. Get the diagnosis right. Get the pre-treatment data right, so that you can really formulate a treatment plan. And once that treatment plan is in place, then, you can decide can I get some of this treatment here, can I go back to my local doctor?

 

Andrew:

Well, I think that’s really critical. So, you are both in really big cities. Our largest, New York, Houston. And there are choices of what hospital you go to or what clinic you go to. Some may be in a more suburban or rural area. But it seems like, if this is suspected, if you can get with this changing landscape, at least a consultation or even your community doctor calling one of these folks to have a plan, an architect plan, even if the community doctor is sort of the general contractor, if you will. But there’s a lot –

 

Dr. Ritchie:

But I want to say something about that a little bit.

 

Andrew:

Sure, please.

 

Dr. Ritchie:

These are all very new drugs. And leukemia patients need a lot of care.

And we don’t really know what we need to know about a drug, until a drug is approved, and it’s being used widely. So, it is something that community doctors should confer with people who have used the drugs. And probably the most impressive abstract that I have seen at ASH this week involves really our ability to develop these sorts of drugs where there was an abstract looking at patients who had FLT3 mutations and how many leukemia patients we have every year in the United States who have FLT3 mutations. Looking at the number of trials that we have open for FLT3 inhibitors and now combinations of FLT3 inhibitors with some of these other drugs.

And looking as to whether or not we have enough patients. It’s very sad, in this country, that only five percent of adults are participating in clinical trials.

So, the ability of our leukemic world to develop drugs that are actually going to improve the quality of life and improve the treatment of these diseases has depended on that very generous five percent of the adult population who is enrolled on clinical trials. This contrasts greatly with children. The Children’s Oncology Group manages to enroll about 50% of children in this country on Children’s Oncology Group studies. And the overall survival of children, in every single malignancy where the COG trials are open are superior to adults’ overall survival.

So, now that we have these drugs, we want to hone in and find ways to make these drugs even more effective. The IDH2 inhibitors are about 40% effective CRs. But it would be nice, if we could figure out a way to combine it with something else and make it 80%.

 

Andrew:

CR, complete remission.

 

Dr. Ritchie:

To make it 80% effective. And the way we are going to do that is by enrolling people on clinical trials.

 

Esther:

But it sounds like the onus is really on patient and their care partners to say hey, if I’m in a rural setting, and I’m not near one of these major centers that I want to have a consultation. I want you, doctor, in my city, and consider a trial. It’s a big responsibility.

 

Dr. Kadia:

Absolutely. I think you have to be an advocate for yourself. And I’ve seen patients, when they’re first diagnosed, their head is spinning. It’s a scary, scary thing. You Google AML, and it’s not a fun thing to read.

 

Esther:

No.

 

Dr. Kadia:

So, their heads are spinning. So, this is a really good time for the family, the caregiver, the friend to come and support that patient and say, look, I got you. I’ll go with you to the doctor’s appointment, and I will advocate on your behalf. And you will advocate on your behalf to say, look, you’re my doctor. You’ve been my dad’s doctor.

 You’ve been my cousin’s doctor, and I love you. But I think that I really want to get a specialty opinion from a disease specialist who treats this really, really rare disease that happens to be really aggressive. And where there’s been so much development, just in the last two to three years where things that we used to do before, we don’t do anymore. It’s just not the case. And people get afraid of clinical trials. Well, I don’t want to be a guinea pig. But it’s not necessarily a guinea pig. I think, you can really ask the doctor that you’re seeing what does this clinical trial entail. Am I going to get a placebo?

Am I going to get standard treatment? And what you’ll see, as far as I know, is many of the trials, most of the trials in AML and leukemia these days, are full treatment trials where they’re studying potential combinations and things like that. And really, get to know your risks, before you sign the consent.

 

Andrew:

You referred to people Googling it and whatever. So, Dr. Lee, given what you know and what you’ve been hearing at this meeting like at the convention center next door, would you say that this is changing so much that, probably, what you’d see in a general write up from last year or the year before on AML, is out of date?

 

Dr. Ritchie:

Then, maybe don’t Google.

 

Dr. Lee:

Absolutely. I think Google is very dangerous because a lot of times, your information is based on how updated it is. So, if you have so many drugs that are approved, and whatever you look up is not updated, according to that, then, it’s very outdated. So, I think Google can be very dangerous.

 

Esther:

So, what should a patient do? So, God forbid, something happened with AML, in our family, Andrew or somebody else. What’s the first thing that family should do, in terms of trying to get enough information?

 

Dr. Lee:

I think, for AML, what’s very important to know is that there are two general behaviors of AML. One is something that needs to be treated right away, as in the same day. Typically, those kinds of patients have a very high white blood cell count, and they’re more symptomatic. So, in those cases, I would advocate that you do not have a lot of time to shop around.

So, if you are really far away, you need to do what you can to treat the disease first. Assuming you’re pretty stable, if your blood counts are not proliferative and changing, you do have time to ask for an opinion. And I would, like anything else in medicine, I would go to a person who treats a lot of the condition. AML is not a common disease. And treating an AML patient requires not only giving drugs but a lot of supportive care. So, you need to go to someone who sees more AML patients. So, that’s what the patient needs to advocate.

So, the first question the patient should probably ask a doctor is how many patients of AML have you treated. And is there someone who you know who has expertise in treating AML? And given the acute nature of things, for us, when patients call, we often squeeze them in same day.

Unlike other kinds of cancers that move slowly, we often see patients on a very short notice because it’s an acute leukemia.

 

Andrew:

Decisions have to be made fast. So, we’ve talked a lot about the family role, whether it’s somebody your same age, and you’re an older person, or the adult child, you can play role the terror, as you referred to, that comes with the diagnosis. So, it sounds like it’s important to sort of pick yourself off the floor, identify a team or consulting healthcare team members who have expertise in the field, to make sense of this IDH and FLT3 and all of the different stuff, and, hopefully, have insurance support, so you can get the testing that’s right for you.

Now, with all of these different drugs, if you find that one is not working or no longer working, with this whole array of treatments, is there something else that probably you can switch to, Dr. Kadia?

 In other words, you’re not out of choices.

 

Dr. Kadia:

No, you’re not. And one of the great things about having these trials and having these new drugs approved is now, we have so much more in our toolbox than we used. Before, like we said earlier, we had two drugs. We had a anthracycline and cytarabine, there’s two types of drugs. And we just used those. We combined it with other things. But it was really the same kind of backbone. But now, you have IDH inhibitors. You have FLT3 inhibitors. You have this drug, Venetoclax, which has shown remarkable response rates, with a low intensity chemotherapy that’s tolerable to people who are 60, 70, 80 years of age.

And so, even if you did not respond, or if you responded and relapsed after your first AML treatment, there’s not a significant loss of hope. You say no, there are other things available. There are many drugs in development. There are many clinical trials. And very often, some of the best care you receive is on a clinical trial because you’ll have a research team and research nurse, in addition to your doctor, who is constantly monitoring, following every single side effect that you have, trying to address every question you have because it is regulated very closely.

So, there are many options. And, certainly, many of the academic centers and even certain other organizations now are offering these trials.

 

Dr. Lee:

One thing that is extremely important for patients to realize, actually, for clinical studies, is that each individual patient is not a statistic. So, let’s say a drug only has 20 or 30% response rate. You don’t actually know, a lot of times, if you’re going to respond or not until you take the medicine. But if you happen to fall under that 20 or 30% that works, it doesn’t matter what that success rate is. But you have to make the steps to try. And that’s what’s the most important thing about treating AML patients.

 

Dr. Ritchie:

I want to mention a couple of other drugs, which have been approved that we haven’t talked about. One is Vyxeos, which is a drug, which is the anthracycline or cytarabine, and Daunorubicin that’s enclosed in a fat globule.

 

[00:36:05]

 

And it’s given differently. It can be given twice a week, for example, or three times a week, depending on what the decision is of the clinician. And it can be given on an outpatient basis. You usually do have to come into the hospital, at some point in time. But unlike normal 3+7 chemotherapy, you may even keep your hair with this. But that’s an option for someone who fails some of the upfront drugs, potentially, or has myelodysplastic syndrome, which is a type of pre-leukemia that develops into acute leukemia.

And it looks like, in these pre-leukemia patients who develop acute leukemia who have myelodysplastic syndrome, it may be a very effective drug. We also have, back in the tool box, Gemtuzumab, Ozogamicin, which is also known as Mylotarg, which was a drug originally approved for older patients who fail standard chemotherapy.

 And it’s an antibody, which binds to an antigen on the leukemia cell called CD33. And it’s connected to an antibiotic called Calicheamicin, which can be enclosed into the leukemia cell and kill the cell. This drug was taken off the market for a period of time because of certain liver abnormalities and has been brought back onto the market. The dosing schedule has changed somewhat. But it’s another option. And it’s an immunotherapy option, which we can use for patients who may fail original therapy.

We also are combining it, in younger patients, with standard chemotherapy who may have a better sort of favorable karyotype or their chromosomes have a more favorable response to chemotherapy that we combine that antibody with regular chemotherapy for a better outcome.

 So, the tool box is really expanded. And I think we’ve talked now about all of the agents.

 

Andrew:

We’ve left one area out though, and that is transplant. So, first of all, I’m living with myelofibrosis and know that there’s a percentage of people who progress to secondary AML. And before, you didn’t have much for us, maybe transplant. And also, other primary AML people who would go to transplant. So, where does transplant fit in, whether it’s primary AML or secondary AML or other drugs for secondary AML? Why don’t you take the transplant first? Where does it fit in?

 

Dr. Ritchie:

Well, we look at a lot of things, when we look at an AML patient. We’re looking at their age and their fitness, what their comorbid illnesses are. We look at their disease. We look and see what are the chromosomal abnormalities that we see, in this particular leukemia.

 And we group them according to favorable risk, people that might respond well to chemotherapy alone, people with intermediate risk where they may or may not have a good response to conventional chemotherapies, and poor risk. We are now also doing the molecular testing. So, we do that 50 gene or 80 gene test where we see what mutations there are, in the person’s leukemia. And we put all of that information together to see what we think the prognosis of the patient is.

So, if the patient has already had heart failure and has had bypass surgery, and they have diabetes that’s not on good control, and they have an unfavorable AML that we would transplant, we may not refer that patient to a transplant consultation because we don’t think that they’re strong enough or fit enough to get through a transplant.

 But my 79-year-old tennis player who has been playing tennis every single day, and the only comorbid illness is hypothyroidism, and they have an unfavorable mutational panel or an unfavorable chromosomal karyotype, then, that patient I would refer to a transplant consultation for cure.

 

Andrew:

Okay. And then, secondary AML where my understanding is some of these drugs may help someone like me, if I progressed, from myelofibrosis. I don’t know whether –

 

Dr. Ritchie:

Secondary AML, if you were a fit person, I think most of us would send you for a transplant consultation.

 

Dr. Kadia:

I think the bottom line is we look at two things. We look at the risk of the leukemia and the risk for the patient. So, we look at the disease and the patient. If the disease is high risk or even intermediate to high risk, we consider them candidates for transplant. Then, the next step is fine, we think you should get a transplant.

Would you do well with a transplant? Is the morbidity and mortality rate going to be high, in your case, or is it going to be low? If it’s going to be high or even intermediate to high, then, we can’t do a transplant. We shouldn’t do a transplant, unless we mitigate some of those factors. If the risk is low, then, that patient should try to get a transplant. Then, there’s the whole thing of do we have a donor available. A donor is, typically, a sibling who is a match. We also have national marrow donor program, which you can get an unrelated match. Occasionally, we do something called a haploidentical where you can get a son or daughter or mother or father to be a match.

Those are probably less likely in older patients because they’re a little bit tougher. And we do those more in younger patients. But there are many options for transplant. I don’t think it’s off the table.

 

Dr. Lee:

One thing to be very clear about transplant is that it’s usually an option, once you get rid of the disease. So, it’s not something you go into, when you are first diagnosed.

 

Andrew:

You’re going to knock it back with the drugs we’ve been talking about.

 

Dr. Lee:

Correct. So, transplant is a modality to really keep the disease from recurring.

So, one thing that is very important that is coming out these days, with ASH and other meetings, is importance of how we measure disease, after treatment, before we go to transplant. And increasingly, there’s a way we’re getting more sophisticated into measuring how much disease you have left over, after induction therapy. And it’s called measurable residual disease, MRD. And you can go deeper and deeper and look, and there’s actually data showing that less disease you have, or if you don’t have any disease, you better after transplant. So, one important thing the patients should remember is that it’s very important to try to eradicate your disease, before you go proceed to transplant.

 

Andrew:

Let me see if I’ve got this right then. So, if you can, you’re going to do this testing to see what version of AML do you have, by these panels of genomic testing.

 

 

Dr. Ritchie:

And the karyotype, the chromosomes that are inside of your leukemia cells.

 

Andrew:

Chromosomes, okay. And then, you’re going to see are there drugs that line up with that that can knock it down to minimal measurable disease? Are you a candidate for transplant that can take it further and maybe give you a longer life? Is there a donor? But for people who are not candidates for transplant, Dr. Ritchie, are we just saying there’s not as much hope for them?

 

Dr. Ritchie:

I like to tell my patients that there is always hope. The issue will be, for these patients, that they will, eventually, need to enroll in clinical trials of new drugs and new combinations, to try and keep their leukemia in remission or to treat a relapse of their leukemia. Although we have all of these new combinations, one of the things that we haven’t really established is, when you fail one of these, and you have a relapse of your disease, what is the next best step?

We don’t really know it for any of these drugs. So, clinical trials become very, very important and really the key to a longer life for those people who are not transplant candidates.

 

Andrew:

That’s for ASH –

 

Dr. Lee:

I definitely agree with Dr. Ritchie. I have one example. I have a patient in her mid-80s. She was diagnosed more than three years ago. And she had a very aggressive leukemia that did not respond to the Decitabine. And she was actually very sick and had a lot of heart issues. She happened to have an IDH2 mutation, and we had a trial. So, we gave her the drug. And more than three years later, she’s still taking the drug, has a completely normal blood count, and going about her business. And she remains in remission and ongoing.

So, back then, we didn’t know how good the drug would be, of course. And we had a clinical study, and she enrolled. And you don’t know, when you have clinical study, how well it’s going to work. So, it’s very important to keep an open mind and be proactive about it.

 

Esther:

If one relapses with AML, in that scenario, do they need to be then retested to the –

 

Dr. Ritchie:

Yes.

 

Esther:

Because I know, in some of the other leukemias, that’s the case.

 

Dr. Ritchie:

The NCCN guidelines really recommend that there is a mutational panel done at diagnosis. But if we’re going to send someone to transplant, there’s a lot of sort of disagreement about how you measure minimal residual disease. But one of the things I think most people are beginning to have a consensus about is repeating the molecular panel to see whether or not we still see those molecular abnormalities, in addition to other things.

 

Andrew:

It’s the driver gene.

 

Dr. Kadia:

Exactly.

So, I think, what we realize is that this is a disease that’s constantly evolving. So, we hit it with chemotherapy. It evolves to progress. We hit it again with something else, it evolves. So, the evolution happens either through chromosome abnormalities or to mutations. So, it’s important to recheck some of these mutations to see now, hey, they didn’t have the FLT3 before, but now they do. Now, we can target it with something else.

 

Esther:

It’s kind of wily, isn’t it?

 

Dr. Kadia:

Exactly. It just continues to –

 

Andrew:

So, I just want to ask you, just poll you really quickly. So, for our patients and family members who are watching, you’re their barometer on how things are changing in AML and what it could mean for themselves or loved one. Are you especially hopeful now?

 

Dr. Kadia:

I am hopeful. I am optimistic. I’m excited. I think these are great times at AML. We talk about the new drugs that have been up front for patients who are in upfront setting, people who have relapse disease. There’s hope for them. We talked about what do you do if you’re not a candidate for transplant. We’re looking now at things called maintenance therapy where we give induction, we give consolidation.

We can give you something that’s low intensity for a very long period of time to maintain the remission and not let you relapse because, sometimes, when you relapse, you say now, we’re kind of behind the eight ball. But what if we just don’t let you relapse? We give you a maintenance therapy. So, these are trials that we’re doing. I think they’re exciting times. I’m very hopeful and excited.

 

Andrew:

You’re positive. You two?

 

Dr. Ritchie:

I feel that I’m living in a period of a revolution. And I think it’s not just a revolution in acute leukemia. It’s going to be a revolution in all of medicine that, as we learn about these mutations in the blood, we learn things about not only treating acute leukemia but maybe even about other medical conditions. I’m going to give you an example of that. We have learned that patients who have certain of these mutations, if they don’t have acute leukemia and have myelodysplastic syndrome, some of these mutations make for a higher risk of cardiovascular disease.

 So, that, as a physician, I now am really worried about the cardiovascular risk factors of my patients who fall into that category, in addition to their disease. They’re also finding that some of the mutations that we are finding in blood diseases, they’re finding in the brain. So, some of the drugs that we are using for hematologic cancers may be useful for pretty terrible cancer in the brain called glioblastoma. So, as we start to make these kinds of connections, this is revolutionary. This is unbelievable.

 

Esther:

Well, it’s forcing a more holistic approach, too.

 

Dr. Ritchie:

We’re filling in little pieces of the one million piece jigsaw puzzle that really confers the health of a human.

 

Andrew:

And you grew up with it, right? Your father is a physician?

 

Dr. Ritchie:

My father and my grandfather and my brother are all physicians. My grandfather was the first pediatrician in the state of Iowa.

 

Esther:

Wow. That’s quite a legacy.

 

Andrew:

How about you, Dr. Lee?

 

Dr. Lee:

I’m very excited, and I’m very optimistic. We have spent a lot of time talking about mutations. But one area that is emerging and, hopefully, in the next [Crosstalk] few years, that will be powerful in AML is, of course, immunotherapy. The immunotherapy has transformed solid tumors. Every solid tumor, there is some sort of immunotherapy. And we’re not there yet, but there’s a lot of clinical studies looking at how to harness your immune system into treating leukemia. So, we haven’t even hit that yet. But a few years from now, I’m sure there will be new immunity therapies that will be very relevant in leukemia. So, it’s very exciting.

 

Andrew:

So, for the family members –

 

Esther:

We just have to be hopeful and stay on top of it.

 

Andrew:

But I think connect with the specialist. You have your community doctor, if you haven’t gone to the big, academic medical center, with their specialists in this field. Make that connection because you hear the change.

 You hear the need for testing to know what is your specific situation that you’re dealing with. Or if you are coming out of a remission, do you need to be tested again? Yes, to know what’s going on then. What are your options? But thank you so much to our panel. It’s been a great discussion. And thank you for helping, in the research you do, because you’re helping lead the way. And if that helps with brain cancer and some of these other areas, put the pieces of the puzzle together, Dr. Ritchie, as you said, for you’ll be very pleased. And your father and your grandfather and all of your medical people in your family will be so pleased.

Esther, I’m really delighted that we can tell this story. Serious illness, acute illness, but there’s stuff to talk about with your healthcare team. Thank you for watching. We wish you and your family the best. And remember, from Esther Schorr and Andrew Schorr –

 

Esther:

Knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Empowerment Network (PEN) are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.


We thank Daiichi Sankyo and Jazz Pharmaceuticals  for their support.

Ask the CLL Expert – Dr. Richard Furman

Ask the CLL Expert – Dr. Richard Furman

CLL specialist Dr. Richard Furman, Director of the CLL Research Center at Weill Cornell Medicine, answered patients burning questions live in this installment of Ask The Expert.


Transcript

 

Andrew Schorr:

And hello.  Greetings.  I’m Andrew Schorr in southern California, San Diego area, and I’ve been living with CLL for 22 years, so I’m vitally interested in today’s Ask the Expert session, this Patient Empowerment Network program.  We want to thank PEN, as we call it, and also the financial supporters of this program, AbbVie Incorporated and Pharmacyclics, although reminding you that they have no editorial control.  You’ll be hearing from our leading expert in CLL in just a minute.

Over the next 30 minutes or so we’ll get to as many questions as we can.  Remember not to make it too personal.  Let it help everybody in the community.  And also discuss what you learn with your own CLL provider so you get the treatment that’s right for you.  Okay.

Let’s meet our expert joining us from New York City and Weill Cornell medicine, and that’s Dr. Richard Furman, who is the director of the CLL research center in New York City at Weill Cornell.  Dr. Furman, welcome back.  Thanks for being with us.

 

Dr. Furman:

Thank you.  It’s my pleasure.  Thank you for having me.

 

Andrew Schorr:

Okay.  We have lots of questions.  One of them that somebody wants to know about is, first of all, if they’ve been‑‑maybe this is an easy one.  If they’ve been diagnosed with SLL, small lymphocytic lymphoma, is that the same as CLL and what we’re talking about with CLL applies to them?

 

Dr. Furman:

So that’s a very important question, and this is one that I actually think is very indicative of how little we used to know.  So in 1993 we actually had a diagnosis of CLL, chronic lymphocytic leukemia, and a diagnosis of small lymphocytic lymphoma.  And we had patients that were diagnosed with SLL if they had a lymph node sent to the pathologist, or they were diagnosed with CLL if they had a bone marrow biopsy sent to the pathologist.

Clearly, we knew that patients could only have one diagnosis and not two, so in 1994 with the new lymphoma classification system the term was actually changed to be CLL/SLL.  So they really are exactly the same entity.  We don’t actually refer to differences anymore, and the whole, the whole individual‑‑the whole disease should be called CLL/SLL.

Now, an important thing is sometimes people require having a lymphocytosis to meet the definition of CLL, but the truth is both conditions are exactly the same.  Both should be treated exactly the same, and there should be no difference based upon having a lymphocytosis.

 

Andrew Schorr:

Okay.

 

Dr. Furman:

Why this is most important, let me just add, is that there are sometimes people will be diagnosed with stage IV SLL and it’s very important to recognize that these stage IV SLL patients unless they have thrombocytopenia below 100,000 like the Rai stage would indicate really are not stage IV.  So the lymphoma staging system would automatically make them stage IV, and that’s certainly not correct.

 

Andrew Schorr:

Okay.  Good point.  All right.  Here’s a question we got in from Julia and Betty and Shelly and Mark.  They all asked a similar question.  They’ve been on Imbruvica for five years now with success.

Is it working for most people, and what are some reasons why it doesn’t work for everyone?  And then what treatment options do you recommend if they relapse on Imbruvica?

 

Dr. Furman:

So right now I think the most important, there are a lot of prognostic markers available for CLL.  At last count we’re probably up to 115.  What’s most important is in 2018 what are those prognostic markers that really are relevant to the patient, and really as long as you stay as CLL you’re going to be able to have your disease very nicely controlled with our current agents and our novel agents.

So there are certain things that do indicate patients are likely to progress on ibrutinib, not likely progress must but who may progress, and people who might need something more, and that’s where a lot of our current clinical are research is focused.  So patients who have a risk of developing a Richter’s transformation or patients who have a likelihood of developing a BTK mutation that might generate resistance to ibrutinib are the two groups of people that we worry about most.

17p deletion is probably the most important predictor for predicting those patient outcomes.  There are other things that are predictive as well like having a NOTCH mutation.  Those are all readily obtainable prognostic markers that allow us to determine who’s at risk and who’s not at risk for progressing on ibrutinib.  If you don’t have 17p deletion or NOTCH1 mutation you have almost a 99 percent chance of being free from progression at five years on ibrutinib.  And it looks like most of the people who are going to progress will progress within five years.  So I think making it to that five‑year mark is really very‑‑is the most important thing.

 

Andrew Schorr:

Okay.  So if you do progress, what then?

 

Dr. Furman:

So fortunately we have a lot of great agents.

Venetoclax works very effectively in patients who progress on ibrutinib, generates some very, very deep responses and very long‑lasting responses.  So that’s certainly one option.  Another option is to be treated with a PI3‑kinase inhibitor.  So we have idelalisib and duvelisib now approved.  We will shortly have umbralisib approved as well as a novel agent.  We also have a whole array of other agents coming down the pipeline looking specifically at means for progression on venetoclax.  So we have an MCL1 inhibitor which targets the protein that’s likely responsible for resistance to venetoclax.  So all these things are actually currently in clinical trials and certainly will hold a great deal of promise.

 

Andrew Schorr:

Okay.  Here’s a question we got in from Jeff.  He says, for young and fit patients with relapsed disease what are the best combos now and coming.  And I suspect maybe Jeff had received FCR, so if he relapses after FCR, what about that?

 

Dr. Furman:

So my belief is that these novel agents should always be used up front, or if you’ve gotten chemotherapy up front they should be used immediately at relapse.  A lot of patients and physicians have the idea that there’s a benefit to holding back until you really need something, but I believe putting our best foot forward first is always the best approach.  So I always recommend going forward first with BTK inhibitor therapy, followed by venetoclax or venetoclax followed by BTK inhibitor therapy.  And I think so in a patient who has relapsed after FCR it will be ibrutinib or acalabrutinib.  In a patient who has relapsed after acalabrutinib and ibrutinib would then move on to venetoclax.

Now, what I’m really very excited about is the possibility of the combination of either BTK inhibitor therapy plus venetoclax or PI3 kinase inhibitor therapy with venetoclax.

You know, both of these combinations really take advantage of the synergy that happens when you take a BCR antagonist like ibrutinib, acalabrutinib or idelalisib and duvelisib and combine it with a Bcl‑2 inhibitor.  And it really sort of enables us to get very, very deep remissions with actually as short as just 12 months of treatment.  And so those are what we’re currently testing in patients right now and what I hope will be the frontline treatment for patients in the not‑too‑distant future.

 

Andrew Schorr:

Now, one of the things people wonder about is if you take these big guns and put them together could you, like you’ve been able to do with FCR, stop treatment or take a break from treatment at some time.

 

Dr. Furman:

So I’m a big believer in that if something’s working and you’re tolerating it well that we shouldn’t mess with it, but we are currently studying two different processes with relationship to the ibrutinib plus venetoclax combination.  So we’re taking patients who become MRD negative on the combination after 12 months and randomizing them to either just get ibrutinib or to get placebo.  And so that’s going to give us information as to whether or not it’s safe to stop patients on the combination and treat them with nothing long term.  We’ll see, one, how many patients relapse, and hopefully none, and, two, if they do relapse whether or not we can then restart ibrutinib and control their disease.  So this will provide us that important question as to whether or not we’re giving up something by discontinuing the therapy.

We’ll have as our comparative those patients who got ibrutinib plus venetoclax for 12 months and then just remained on the ibrutinib.

And so that will sort of be the patients who will continue on with their therapy, and then the other half will be patients who have discontinued all their therapy.

My belief for going to venetoclax is that you’re going to get almost all of the bang for your buck out of the first 12 to 24 months, so continuing it is unlikely to yield an additional benefit, so I think stopping it is safe.  But, once again, these are the studies that will provide us with those data.

 

Andrew Schorr:

Okay.  Now Maureen sent in a question where they responded to venetoclax and rituximab and they wondered what about testing for minimal residual disease?  They don’t have any lymph nodes or anything, but is that then appropriate to do a MRD test to see how deep the remission is?

 

Dr. Furman:

So the real important question should be whether or not that’s going to impact upon clinical management.

So MRD testing is easy, it’s noninvasive, it’s a peripheral blood test or a bone marrow biopsy, which I guess is only relatively noninvasive, and the information though is really not going to be of use.  So if you’re taking a patient who’s on ibrutinib and you’re going to continue the ibrutinib knowing the MRD status won’t change anything.  Likewise, if you have a patient who’s on venetoclax, who’s going to get a year of venetoclax on trial and then stop, knowing the MRD status won’t change anything as well.  So currently there’s no real reason for doing MRD assessments in patients except for just the ability to know.

Now, one day there’s some modeling that suggests that the time it takes you to reach MRD negativity is half the time you need to be on a substance, an agent, before you can actually claim to have a deep enough remission that you won’t relapse.  So we may one day say if you’ve been on ibrutinib for five years and became MRD negative, then 10 years of ibrutinib is enough and you can stop.  But that’s currently just theoretical and based on mathematical models.

 

Andrew Schorr:

Theresa wrote in, she said, my husband is being treated with acalabrutinib for five months.  He’s doing well, but should he have some sort of testing to know whether he will develop some sort of resistance in the future?

 

Dr. Furman:

So that’s a very important question, and the answer really is, you know, testing for it now isn’t going to be able to change anything.  Right now we would still continue the acalabrutinib until we see signs of clinical progression.  There’s some early data emerging from Ohio State where they’re doing PCR testing on all the peripheral blood of patients, on the peripheral blood of all patients to see whether or not they can detect any of these mutations that lead to resistance.  The problem is you’re still going to continue the treatment until you see the clinical relapse.

And, two, is you really‑‑you know, in essence when you look at the data that suggests that 92 percent of patients who get ibrutinib as a first‑line therapy will remain in remission at five years you’re talking about treating‑‑or testing a lot of people for very, very few people that will likely benefit.

 

Andrew Schorr:

Okay.  So if you have a question now, send it in, cll@patientpower.info, and we’ll do our best to pose it to Dr. Furman.  Okay.

So Beth with wrote in and wanted to know is there work going on on a CLL vaccine?

 

Dr. Furman:

So we’ve been playing with CLL vaccines for at least the past 25 years, and a lot of these vaccines were originally designed to be what we call antiidiotype, meaning they were directed against the antibody made by the cell itself.  Unfortunately, a lot of those vaccines have not proven effective, and we’ve gone through a lot of different iterations.  We’re still trying, and hopefully one day we will have better success.

Right now a lot of our current research is focused on not so much the target that the vaccine should be against but ways to make the vaccine more effective.  Things like using PD‑1 inhibitors, which can actually make the tumors more apparent to the immune system.  Or using things that can actually enhance the presentation of the actual vaccine to the immune system, and that includes everything from idelalisib and ibrutinib to other different molecules that may actually make it more readily apparent.

Now, we do also have some new targets like ROR1, which may prove to be very exciting and interesting, but this is still all very far away from anything that will be approvable.

 

Andrew Schorr:

Okay.  Now, here’s a question we got in from Cerisa, said, my understanding is that most drugs aim at destroying the CD20 protein like rituximab or obinutuzumab, etc.

Well, what about, CD9, CD15, CD23?  Are they not as bad as CD20 in CLL?

 

Dr. Furman:

So the thing that’s really important to keep in mind is only our monoclonal antibodies attack one protein in particular, and so we have obinutuzumab, rituximab, and ofatumumab all of which address or target CD20.  CD20 was the first protein targeted for two reasons.  One is it’s ubiquitously expressed on all B‑cell lymphomas, and so it’s a way to identify a target that we can actually generate one treatment for that will work in a large number of people.

The second is it’s a protein that doesn’t seem to actually get endocytosed or down modulated so that it remains positive in the cases most of the time.  One of the problems with some of the other proteins you mentioned is that they’re not expressed on the CLL cell.

So CD3, CD15, those are not present on CLL cells, but they’re also present on a lot of other cells as well.  The key about CD19 and 20 is that they’re only on B‑cells, and we really can actually do okay without our B‑cells.  And so that way the down side to knocking an out all our B‑cells is actually relatively minor.  And the CAR‑T cells, which are T‑cells taken out and reprogrammed, they’re reprogrammed to be directed against CD19 and 20, so in a way they work like the monoclonal antibodies.

 

Andrew Schorr:

Okay.  Lynn wrote in and asked about transplant in CLL, and I’ve met people who have had transplant, so where does transplant fit in now, and does CAR‑T cell experimental therapy maybe supersede that?

 

Dr. Furman:

One well, one of the things that’s important to keep in mind is that CAR‑T cells are still very novel, and the long‑term efficacy is not yet there, so we still need to do a lot of work to help that.

My belief is allogeneic transplants are very effective but they’re also very toxic and dangerous, and I do believe that they should be avoided if at all possible.  So I am very, very selective in who I refer for allogeneic transplant.

With our novel agents like ibrutinib, idelalisib, duvelisib, umbralisib, acalabrutinib, vecabrutinib, zenabrutinib, the list is just rapidly growing, I almost believe that the patient who really needs an allogeneic transplant will only be those patients who have developed or are at high risk of developing Richter’s transformations.  So I really do believe there’s a very limited role for allogeneic transplant at this point in time.

 

Andrew Schorr:

Okay.  And CAR‑T, you’re watching it.

 

Dr. Furman:

I am.

 

Andrew Schorr:

Okay.  Here’s a question that came in from Mike, and this is the bottom line for a lot of people when they’re diagnosed, and he says, what is the current state of treating CLL for those of us watch‑‑he says wait and see patients or watch and wait.  In other words, is it curable?

 

Dr. Furman:

So right now CLL is not curable.  The way that I would love everyone to start approaching CLL is very analogous to high blood pressure.  So we don’t cure high blood pressure, but if you take a pill a day it’s not going to have an impact on your longevity.  And I believe we’re there for about 75 to 80 percent of CLL patients, where they will be able to get a BTK inhibitor or a Bcl‑2 inhibitor or a combination and they will be able to not have to worry about their CLL for the rest of their lives.

There’s still the 20 percent who are going to develop either a Richter’s transformation or a progression on ibrutinib, and those are people we’ve got to figure out what to do differently for.  But all the others, even though it’s not curable, we can definitely I think keep it from having an impact on longevity.

People on watch and wait who are high risk of progressing and developing a Richter’s or progressing onto developing resistance to ibrutinib, we do have a couple of trials that are very interesting right now where we’re treating people at diagnosis with BTK inhibitors with the hope, because they’re so well tolerated and because they’re so effective, we might be able to have an impact and prevent those patients from developing resistance or developing a Richter’s transformation.

 

Andrew Schorr:

Wait a minute.  So are we looking at what has been the traditional watch and wait period differently now and some people will be treated much earlier?

 

Dr. Furman:

Well, we’re just starting to look at that right now in clinical trials.  So this is very early.  It’s for a very select group of people.

We know from the data‑‑so we have seven‑year data coming out at ASH this year where we’re going to have a group of people who were watched and waited and only when they had evidence of disease progression and needed treatment and got ibrutinib, 92 percent of them were still doing well and free from progression at seven years.  So for those 92 percent of patients we couldn’t do any better.  So it’s really just a very small group of patients who need something extra.

So, yes, we’ve proven I think in a large number of patients that BTK inhibitor therapy might be all that’s necessary, but in everyone else, in those 8 percent we do have studies going on to try to answer how to treat them differently.

 

Andrew Schorr:

Okay.  So we got a question early on about somebody who was asking about should he be taking a statin along with his oral therapy for CLL.  So people have other conditions.  So what about that?

 

Dr. Furman:

So if you have hyperlipidemia you should definitely be on a statin, otherwise, no, you don’t need a statin.  I think it’s important to keep in mind that there was a lot of data generated at one point about statins perhaps changing the CD20 expression on the surface of the CLL cells or making rituximab or other anti‑CD20 antibody therapy more efficacious.  I’m not aware of any data that suggests there’s an impact to statins on non‑anti‑CD20 therapy efficacy, and I think the impact on anti‑CD20 antibody efficacy is actually really quite small and unlikely to generate a significant difference.  So I really don’t believe there’s a need to do anything outside of just treating your lipids.

 

Andrew Schorr:

I promised our audience weeks ago that I’d ask you about this.  So should we have flu shots?  Should we have the shingles vaccine?

 

Dr. Furman:

So, absolutely.  Everyone should definitely get a flu shot each year.  And it’s important to get the flu shot each year because the immunity doesn’t persist.  So I actually recommend people get vaccinated either October or early November.  All right?  So any earlier than that I worry that you’re going to have your immunity peak before the height of the season, and later than that you may not actually have sufficient time to respond.

Regarding the shingles vaccine, so there’s a new shingles vaccine called Shingrix which is a recombinant vaccine, so it’s not a live vaccine, and that’s how it’s different than the previous shingles vaccine.  The previous shingles vaccine was an attenuated or live virus vaccine, and CLL patients really shouldn’t have taken it because it really theoretically could have caused shingles.

Now, the old shingles vaccine was also not very effective, so even though the risk was low with low efficacy there’s really no risk/benefit assessment that puts it in favor of doing.

But the new shingles vaccine actually has been tested in patients post autologous bone marrow transplants, so it’s very effective in patients who are very immunosuppressed, and because it’s not a live vaccine it is safe.  So I do recommend it for everyone.

 

Andrew Schorr:

Okay.  Dr. Furman, so you mentioned it earlier and we’ve heard about a lot of programs, the 17p deletion and I almost think of it as the dreaded 17p deletion, but is that necessarily true?  Pam wrote in, she said, I have the 17p deletion.  What are my options?  So first of all, are all 17ps alike, and then what are the options?

 

Dr. Furman:

So the thing that’s most important to keep in mind when we talk about prognostic markers is they’re really just surrogates for clinical behavior.  And so the answer always is going to be if you have historical data that’s always going to trump the prognostic marker.

So someone who is 17p deleted and their disease has remained stable for the last five years, their disease is stable, and the 17p deletion is not going to be what drives the prognosis.  I think that’s very important because when you look at a curve you’re going to see some people doing well and coming off the curve late and some people doing poorly coming off the curve early.  You know, where they are on the curve we have no idea how to predict.  All we know is that they’re on a particular curve.  So prognostic markers tell us about the population, never about the individual.

Now, with that being said, we do know 17p deletion a lot of it, the percentage of the deletion if you’re above 20 or below 20 does have an impact on how you do overall.  So 20 percent and below, they‑‑patients seem to have a better prognostic outcome than the patients who have 20 percent and above.

With that being said, I do have patients who have 17p deletion in 70 percent of their cells and they’re just hanging out doing quite nicely.  So clinical behavior does trump everything else.

 

Andrew Schorr:

Okay.  So, obviously, most CLL patients are older.  I’m 68 now, but I was diagnosed at 45, which is pretty young, but here’s Matthew who writes in he was diagnosed at age 31 and he wonders, he knows a lot of the statistics but he knows it’s mostly older people.  He’s trying to figure out, well, what’s his life going to be like.  So what do you say to younger patients with CLL today?

 

Dr. Furman:

So, remember, we’ve only had these novel agents since 2010, and so what I really do believe is that we really don’t know how good things are going to be yet.  I think things are going to be a lot better than we ever envisioned, so I am quite optimistic about the future.

We don’t know whether or not a 31‑year‑old could enjoy a normal long life expectancy but if they don’t have evidence of or suggestions that they’re going to have particularly aggressive disease and develop resistance to a BTK or a Richter’s transformation, they could theoretically have 40 years on a BTK inhibitor.  And so that’s certainly what my hope is for the future.

You know, all the survival curves that people talk about and all the survival curves that people show really don’t take into account any of the novel agents, and that’s always very important to keep in mind.  So we do some have data.  As I mentioned, the seven‑year data is coming out from‑‑will be out at ASH, and the seven‑year ibrutinib data really suggests almost a nearly flat curve for patients with CLL who get ibrutinib as a front‑line treatment.

 

Andrew Schorr:

So you mentioned over the years the Rai staging system, and Dr. Rai, the grand old man of CLL.

So how does that apply now?  You know, somebody’s diagnosed with CLL, they come across this Rai staging system, but is that meaningful for them today, or are there new ways of looking at it?

 

Dr. Furman:

So the Rai stage really still drives when we’re going to treat patients.  So patients are still treated based on meeting, you know, the classic indications for initiation of therapy.  So Rai stage 3 and 4, namely hemoglobin less than 11 or a platelet count less than 100,000, really are the two primary reasons why people initiate therapy.  We know that if you watch and wait someone until they meet classic criteria and they have disease that doesn’t harbor one of these high‑risk changes we know that they’re going to do extremely well.  So that’s good news.  Whether or not patients who have these other markers should be treated before they have aggressive disease is on open question.

Now, what I really do think that’s also important to keep in mind is, you know, the watch and wait ideology really came about when we had therapies that were not very effective and also were quite toxic.  Now that we have these novel therapies that are far less toxic and highly effective, maybe the bar should move towards initiation of therapy sooner, but that’s still on open research question and not one that we know the answer to yet.

 

Andrew Schorr:

Okay.  And Bob has had the same treatment I’ve had.  He had Gazyva or obinutuzumab with high‑dose methylprednisolone, and now that was, gee, about two years ago, and now his CLL has started to show up in his spleen and his lymph nodes.  He said, well, can he be treated with the same combination again, or might he move to something else?

 

Dr. Furman:

Well, that’s going to depend on a lot of factors.  Most importantly is whether or not there was, you know, he had received the full dose in which case the likelihood is that with just a two‑year remission I would expect that retreatment would generate a shorter remission this time, and the risks associated with high‑dose methyl prednisolone plus obinutuzumab probably don’t outweigh, or aren’t going to be‑‑the risks are going to outweigh the benefits that would be gained if we’re talking about a response that’s going to last less than two years.  So it would probably be better to move on to additional agents.  And, fortunately, we have so many others that I think it would be a way to avoid resistance and also develop‑‑avoid, actually, the toxicities associated with high‑ dose methylprednisolone.

 

Andrew Schorr:

Okay.  We’ll take just a few more questions, and thank you, Dr. Furman, for sticking with us.  And I relate to this one.  So I did have the obinutuzumab and rituximab years ago, and I developed sort of a history of sinus infections for a while and even some chest congestion and I’ve seen other people write in about it.

Do we have the sinus or the respiratory issues from the CD20 antibody or is it something else?

 

Dr. Furman:

So it’s important to recognize that CLL patients, 75 percent of CLL patients will develop hypogammaglobulinemia, and that hypogammaglobulinemia is probably most of the cause of the chronic sinusitis, chronic bronchitis, sort of that‑‑those issues with having the constant drainage.  So I do believe that CLL in and of itself is certainly the first factor that impacts upon that.

The anti‑CD20 by itself will also cause a lot of those problems as well, so the two together are just a double hit.  But we do know that CLL patients, totally regardless of their prior‑‑regardless of their prior treatments will run into those issues.

Now, with that being said, what people often forget is the most common cause of a chronic sinusitis in anyone, even a CLL patient who’s gotten obinutuzumab, is still going to be a deviated septum,  or it’s going to be a blocked sinus channel, so I always recommend and I always insist on all my patients being evaluated by an ear, nose and throat doctor first just to make sure there isn’t something anatomical that could be fixed.

 

Andrew Schorr:

I went to an ENT the other day, and also I’ve been doing‑‑and I know my Dr. Kipps here is urging me, I’m doing the nasal wash and all that stuff, just trying to have sinus hygiene, if you will, working on that.

Okay.  Couple more questions.  Aukie wanted to know, and we’ve talked about this in the CLL world forever, should he be taking a green tea extract?  Is there any validity for that?  What do we know?

 

Dr. Furman:

So my belief is no.  I think it’s important that we have a lot of alternative medicines, medicines that have been studied, and until they show evidence clinically I do believe that it’s important to actually stay clear of them, and there are a couple of reasons why.

So a lot of things work in the laboratory, but that doesn’t mean they’re going to translate into working clinically.  And a lot of the medications that are sold as alternative medications or homeopathic medicines are unregulated and can make claims that aren’t substantiated, but they also don’t have their products necessarily vetted.  So we’ve had a number of examples of people who have been taking a root or have been taking some leaf that’s turned out to be laced with amphetamines.  So a leaf that claims to enhance your energy output, absolutely, if it’s laced with amphetamine will certainly be able to accomplish that.

So it’s important to keep in mind that anything that’s made naturally or that occurs naturally doesn’t actually get regulated the same way as pharmaceuticals.  There was also a change in the laws in the 1990s where anything that was natural didn’t have to be tested and approved by the FDA, so the claims that they make‑‑like Tony the Tiger can say that Frosted Flakes are great without proving that in a randomized controlled clinical trial.  Because it’s a naturally occurring substance it can make claims that aren’t necessarily substantiated.  I do worry about that.  And there are some definite cases of patients coming to harm from taking medication‑‑from taking supplements that weren’t well regulated.

 

Andrew Schorr:

So, as you know, so many of us complain about fatigue with CLL.  What can we do about that?  Is there any medication or something you feel comfortable about as a supplement that could help with that?  Certainly, we’ve been telling people exercise is a good thing and can give you more energy, but what do you tell your patients when they talk about fatigue?

 

Dr. Furman:

So this is actually a very common question, and I really do believe it’s very important to remember that having CLL doesn’t protect you from the things that befuddle the rest of us.  So the most common cause of fatigue in a CLL patient is not going to be the CLL but it’s going to be the same thing that befuddles the rest of us.  So it’s poor sleep hygiene.  It’s not sleeping long enough.  It’s all those things that really should be addressed first and foremost.  So we see a lot of sleep apnea that’s undiagnosed.  We see a lot of people who are just not sleeping long enough.

If we’ve ruled out everything else and a patient seems to have progressive disease, yes, there are definitely patients with CLL whose fatigue is related to the CLL, but I’m a big believer that fatigue related to CLL should only be present in a patient who really has active signs of CLL.  So if someone is on watch and wait and their lymphocyte count is not changing and their lymph nodes are not enlarged, their fatigue is not going to be related to their CLL.

But if someone’s lymphocyte count’s climbing and their lymph nodes are growing then certainly their fatigue might in part be related to their CLL.

 

Andrew Schorr:

Okay.  This has been like being on a game show.  I keep throwing things at you.  I want to thank you for all your time.

Folks, we’re going to let Dr. Furman go, but we will be doing other Ask the Expert sessions and doing some live broadcasts in from ASH.  ASH, you alluded to, Dr. Furman, always has more coming out, more longer range studies, combination information.  So just to wrap up with, for those of us living with CLL, and, thank god, so many of us long term, me, 22 years, are you very hopeful that you have more options for us now no matter what our CLL situation is?

 

Dr. Furman:

I really do.  I think we have some amazing options now.  We have also the data that our current crop of novel agents really can be safe and effective long term, and that’s what I really think is so important to be cheerful about.

And in those patients who do progress we have a whole crop of other agents that will prove to be hopefully effective in those situations.  But I think it’s going to be the‑‑you know, the home run though is going to be the combination of BTK and Bcl‑2 inhibitor therapy or PI3 kinase and Bcl‑2 inhibitor therapy because in those situations I really do see patients getting very, very deep remissions that I hope will be extremely long lasting.

 

Andrew Schorr:

Think about it, folks.  I mean, I got FCR, a three‑drug combination, in 2000, 18 years ago, and it worked for a long time.  So the idea of combination therapy has worked well in cancer therapy hitting those cancer cells in multiple ways.  Dr. Furman, thank you so much for being with us today.

 

Dr. Furman:

My pleasure.

 

Andrew Schorr:

Okay.  From Weill Cornell.

And I just want to mention for our audience, remember we’ve got a lot coming up.  On Wednesday, November 28, we’re going to understand the ins and outs of watch and wait for those of you who are in that situation.  From the big ASH meeting in San Diego‑‑yay, I don’t have to get on a plane to go anywhere‑‑we’ll be also doing live broadcasting so be sure to be signed up for that.

And then on December 5th we’re going to talk about the financial issues because, as Dr. Furman talks about, combining these oral therapies, these are expensive, and so what support is there for you so you get the combination should you need it and it’s affordable.  So keep an eye on that.  Go to the Patient Empowerment Network’s website, powerfulpatients.org, and take a look at what we have on Patient Power as well.  Thank you so much, Dr. Furman.  Thanks to our audience and stay tuned for what comes out of the ASH meeting.  I’m Andrew Schorr.  Remember, knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Empowerment Network (PEN) are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Patient Cafe® CLL – October 2018

Dealing with a Mid-Life CLL Diagnosis

Patient Cafe® CLL – October 2018 from Patient Empowerment Network on Vimeo.

Four Chronic Lymphocytic Leukemia (CLL) patients got together to share their story and advice on dealing with a mid-life diagnosis, and how that can affect your personal and professional life.


Transcript:

Esther Schorr:
Hi there. Thank you for joining our Patient Cafe today sponsored by the Patient Empowerment Network. I’m Esther Schorr, and today I’m meeting virtually with a group of CLL patients, chronic lymphocytic leukemia, who are all facing this diagnosis during their middle years. So of course there’s no really good time to be diagnosed with something serious or diagnosed at all, and it’s never easy and it’s never welcome, but in our middle years the career ball, your personal life direction, the people that you indirect with, the relationships you have are already pretty well in progress and a diagnosis can feel as though personal and professional life kind of had a monkey wrench thrown into it and that your plans for life could be derailed.

Our guests today are going to share their stories and advice about how they’ve been able to deal with a midlife diagnosis. So just before we start I want you to know that this conversation is never, would not be a replacement for medical care, medical advice. Each patient’s situation is unique, so I really encourage you to consult your own doctor, your own medical team for the treatment that’s right for you.

So first of all I just wanted to tell you a little bit of where I fit into this conversation. My husband, Andrew, who you’re going to meet in a second, was diagnosed with CLL in his mid-forties, and at the time we had two small children.

Also, we were in the middle of growing a fledgling business that then became what we do now in educating patients. And we were devastated. It was scary. We didn’t know what the complications long term were, we even wanted to have a third child at the time, and certainly, like most people, we didn’t know anything about CLL. We didn’t know. And the word “leukemia” was very frightening. We were very lucky at the time. We had supportive family and friends, and we found great medical care through networking with other people on the internet, through online support groups, etc. And ultimately Andrew got through a clinical trial, went into it, went through the trial and had a long remission, and we’re very, very thankful for that.

As a care partner, I will tell you it’s taken years of ups and downs for me emotionally to come to terms with the fact that we can’t really live our life based on what‑ifs.

And we’ve gone on together with our friends, our family, and we just live our life. We now live in southern California near the beach with our dog, and we have three grown kids who are very supportive, and‑‑but we’ve learned a lot along the way. And so I’m hoping that this discussion will help those of you that may be in similar circumstance to kind of come to a place where you can move on with your life and feel empowered. Is that’s my story. I want to have each of our guests introduce themselves. So why don’t start. Jeff, Jeff Folloder, why don’t you start.

Jeff Folloder:
Hi. I’m Jeff Folloder from Katy, Texas, which is just outside of Houston. I am a CLL patient, and I am also a Patient Power advocate, champion, evangelist, pick one of the terms, whichever one you’re comfortable with. I was diagnosed at 46 years of age.

I absolutely, positively was not expecting to hear my doctor say something’s wrong and you need to go see a specialist. Walked into the specialist’s office, saw a bunch of old, sick people in there, said this isn’t me, and the next day I was told, yes, it is. So my diagnosis did absolutely come as something of a huge shock. It was like a sucker punch in the gut, and it took me a bit of time to figure out has comes next.

I was very fortunate to get connected with some folks here in Houston who got me enrolled in a clinical trial after two, two and a half years of watch and wait. I got six and a half years of rock solid remission out of my clinical trial. This past July I have recently relapsed, and I’m looking at it right now quite frankly as no big deal.

I’ll get treated when it’s time to get treated. In the meantime, I’m driving all over the country, I’m doing all kinds of things. I’m living life to the fullest, and it’s actually okay to take a nap.

Esther Schorr:
Thanks, Jeff, that’s perfect, and we’ll talk more about that journey for you in a minute.

Jeff Folloder:
Absolutely.

Esther Schorr:
Let’s try the other person, Andrew, and then we’ll hit Michelle and Jeff.

Andrew Schorr:
Esther, thank you for hosting this program. So you recall vividly I had a routine blood test at age 45, and the doctor initially said when he tested my blood, oh, you’re probably fine because I had been getting some nosebleeds, and then he called me, and he said you’re not fine. What is it? Leukemia. What is leukemia? I wasn’t even sure it was a cancer. And I also didn’t understand the difference between acute leukemia and chronic leukemia. And so what knowing I’d heard somewhat about acute leukemia then, Esther, you and I, remember, we walked in the park in a sunny spring afternoon near Seattle, and I thought I was dead. And I was saying at 45, we have two kids, hopefully you’ll be well provided for, and I had life insurance. Is that it?

Well, fortunately, it hasn’t worked out that way, and I got a long remission, pretty long, Jeff, 17 years, actually and then needed CLL treatment again many months ago, and that’s worked well. So just like what Jeff said, knocking it back, going on with my life. We had a third child, but when I was first diagnosed I thought it was over, but now looking back I know it was really just the beginning, but maybe seeing life a little differently but living.

Esther Schorr:
You thank you. Thank you for that, Andrew. Michelle, tell us a little bit about you.

Michele Nadeem-Baker:
Hi. I’m Michele Nadeem-Baker, and I’m a Patient Power advocate as well and a Patient Power patient reporter. And I have to say, as Jeff had mentioned, I was in shock, absolute shock, no awe, but in shock when I was told that I had CLL. My PCP like everyone else’s had said that my white blood counts were a bit off, told me to see a hematologist, and I was very naive not realizing hematologists generally went along with oncology.

Went to the local medical center when I lived in Miami and was not told I had CLL, and then I was called back in for when some other test results came in, the flow cytometry came in, which I now know but at the time had no clue what that meant, had no clue what the doctor was talking about. He didn’t even‑‑he said I had the C word. He didn’t even say cancer. And then he said CLL. I had to ask what that meant.

And that’s why I’ve been such an advocate for communicating better for patients because I was a bit dumbfounded as well as in shock. He had no information to give me, and I have since tried to learn a lot and become an advocate for other patients. Andrew is the first person I met with CLL. I reached right out to him, but it was very tough.

I had been married at that point for only two years to my now husband, and it was a real, real shock. My career went into a tumble, a turmoil, and it got put on hold for a while. So I was in watch and wait for about three years. In that time I moved back to Boston, so I could be seen at Dana‑Farber. And as both Jeff and Andrew said, life does go on. You just‑‑you have to get into kind of a new step and a new rhythm, but life does go on thankfully and thanks to all the research that’s been going on.

And I’m still on a clinical trial. Still in remission. Fingers crossed that will continue. And I’m happy to chat about anything that will help.

Esther Schorr:
Right. We’ll have a lot to talk about, I think. Thank you, Michelle. And the other Jeff, tell us a little bit about where you’re from and where you’re at now.

Jeff Brochstein:
Will do, Esther. Thanks again for having me. Really, my story follows much of the same path. Diagnosed at a fairly young age, 38 years old. I discovered a small lymph node in my neck while I was washing up one Sunday night back in late 2012 and got it checked out and couple months later high white blood cell count, and another high white blood cell count when I was tested again, and I was diagnosed. And really from there I just buried myself in just doing all the research and all the data gathering that I could.

Maybe about three, four months after diagnosis I discovered Patient Power. I found Andrew. I gradually started corresponding with him. From that point on, the next four and a half years I was in watch and wait until probably late 2016, early 2017. Reached out to Andrew again at that point. We had a conversation about FCR, which my doctors here in Atlanta had been talking to me about. Decided to go to MD Anderson after seeing some of the videos on Patient Power of Dr. Keating, Dr. Thompson. Went there to see actually Dr. Thompson who had mentioned ibrutinib and some of the other targeted therapies that had been just approved for frontline. And came back to Atlanta and my doctor and I kind of came to the conclusion that maybe starting with one of the targeted therapies was probably best me being unmutated.

And started ibrutinib March 2017 and lymph nodes went away after a week and kind of been in remission pretty much ever since and everything’s going well.

Esther Schorr:
Thank you, Jeff. And all of you, there are some recurrent themes here that we’ll talk about, but obviously this whole idea of coming into the middle of your life when a lot of things were already in play was something that you had to pretty quickly say, okay, what am I dealing with and then figure out how do you continue with what you were already doing and how does it fit in.

So I want to dig into that a little bit more, and I’d like to start with you, Michelle. And tell me if I’m wrong, but my understanding is that when you were first diagnosed you were really in a pretty high‑level executive position in PR and communications, and how did you cope with the diagnosis in the middle of a very busy professional life?

Michele Nadeem-Baker:
It was not easy, and that part still isn’t easy. I’ve been trying to still come to terms years later with that. I was at a height of my career in a dream job, and I knew that I could no longer stay in that job because it meant staying in Florida, and I needed to move back home where my family was and my husband was. We had a long‑distance marriage because of career. It made me realize what’s really important in life, and that’s to be with family, but I was able to then continue using parts of my career in other ways and to help, as Andrew did. You’re doing very similar things yet now you’re doing it to help patients, and that’s what I’ve been trying to do. You’re a great mentor, Andrew. And so it, yes, it was very difficult when it comes in terms of that and as well as income and being used to being a high income earner and then not having that.

Esther Schorr:
So can you share how you made that transition? It sounds like you moved closer to family.

Michele Nadeem-Baker:
I did.

Esther Schorr:
And career‑wise what helped you make that transition?

Michele Nadeem-Baker:
I had to give up my job and my career. And I was well known in Florida, and I moved back up to Boston. I needed to remake connections from when I lived and worked here. And I’ve been consulting ever since versus within a company and a full‑time job. So trying to use what I do best, just communicate and go and help others. And what’s been happening is I found that it’s been mostly in life sciences and related fields.

Esther Schorr:
Okay. Thank you. You know, you mentioned Andrew. Andrew, did you want to speak a little bit about that transition that you had to make because we were at the time sort of building‑‑well, sort of. We were building a business and a family at the same time.

Can you share a little bit about what it took for you to make the change that you did?

Andrew Schorr:
Sure. Well, I think‑‑we were fortunate. We were already working in health communications. Michelle has sort of made that transition, and Jeff too actually is spending a lot of time doing that. So you kind of‑‑for us, you know, Esther, you and I think accelerated in what we were doing. I think for Jeff and Michelle they’ve sort of joined in where you can leverage what you’re learning as a patient to help others, and that’s very satisfying. And fortunately now with the internet we can to some degree do it on our schedule.

So sometime we’re tired. Sometime we’re distracted‑‑not distracted, that’s not fair, but we have doctor visits. We have bone marrow biopsies. We have other things. I get IVIG, monthly infusions. So how do you juggle all that?

And I think we learned to do that. At least that’s what I’ve done, and I think it’s been satisfying that we can communicate with others, and it’s part of who we are. Never wanted the diagnosis of CLL, no, no, no, but if you have it how can you go forward and do that? And I know both Jeffs are involved in helping other patients as Michelle is too, so that’s part of it.

Esther Schorr:
Thank you. So, Jeffs, any additional comments or points you want to make about this?

Jeff Brochstein:
As someone who is probably I think out of everybody here who is maybe less in a patient advocacy role, I mean, I’ve done it a few times, I’m always open to who, you know, Andrew sends me in terms of young people who are diagnosed who want to speak to someone with whom they can share experiences with, you know. I’m an IT projects manager. It’s not necessarily boiler room type work but it’s still, it’s pretty fast paced.

It’s pretty intense at the times. One thing that I’ve really experienced in terms of just first firsthand trying to deal with having CLL and making all the appointments, the bone marrow biopsies, the routine blood work, you know, I tend to‑‑I don’t openly communicate my condition to everyone at work, but I’ve been lucky and I’ve been blessed to have pretty decent managers who I directly reported to ever since diagnosis, and they’ve been just very accommodating and understanding. And in some regard they have to be, but I’ve been lucky enough to find that in the workplace, and that’s been really, really great.

Esther Schorr:
Okay. And actually that’s a great segue because the next thing I was going to ask about was how each you have handled communication with family and friends about the diagnosis. That’s a very personal thing. There are some people who are way out there and, gee, we don’t know anybody like that, but it’s a really personal thing. So maybe Jeff, Jeff Folloder, how did you handle that initially, and has that changed over time?

Jeff Folloder:
Well, I never hid my cancer diagnosis from anyone. I believe in the very first Patient Power event that I did I talked about the mistake that I made with my cancer diagnosis. I told my family. I told my wife. I told my daughters. I told my friends. But I kind of sort of forgot to tell my daughters that my CLL wasn’t considered hereditary, and my daughters kind of sort of flipped out for a significant period of time until I learned, wow, I should probably let them know what exactly is going on so that they can stop worrying a little bit.

And I did. And so now I make sure that people understand what it is that I think they need to hear. I don’t tell everyone the gory details of my CLL experience. Some people I tell, yes, I’ve got cancer. I’m a survivor, or I’m in remission, or I’ve relapsed. And the people I care about, I make sure they understand what’s really going on and how it affects me.

And at this point some almost nine years after diagnosis, and I know this is going to sound very counterintuitive, cancer gave me an awful lot of opportunity. I would have not had the ability to pull the hand break up on my life and reprioritize everything without a cancer diagnosis. I was moving too fast. Concentrating on the wrong things. Spending my energy on the wrong things. Now I focus on the right things.

And as Andrew is fond of saying, I’ve learned how to live well, and that’s because I’ve learned from everyone involved with Patient Power.

Esther Schorr:
Wow. Well, thank you. Michelle, Jeff B, Andrew, other commentary about how you communicated or chose not to communicate?

Michele Nadeem-Baker:
I did the opposite. Because‑‑probably because my career included crisis communications I was afraid if once I let out the info it would be career suicide, which is a very sad thought when you think of society. But instead now I’m trying to change that, that thought has that’s out there, that you still can be viable when you have a cancer diagnosis, which everyone here is proof of. But I was very afraid of that, that that would ruin my career.

As a matter of fact, I did not come, you know, out until I started in the infusion room and reported for Patient Power from it each time.

I was in infusion with the FCR part of my trial. So it dawned on me that in the past I had worked with the American Cancer Society and convinced people to come out about their cancer and explain to other patients. And I felt somewhat like a hypocrite that I did not, and I realized it was time. It was really time to do that. And it wasn’t only about me. It was about others as well. And that really helped empower me a lot.

And also as Jeff has said and I was saying before, it really does help you prioritize what is right, the right things to be spending your time on because I was on the hamster wheel of career and never sleeping, and this forced me, I had to. And as you said, naps aren’t a bad thing. I had to learn that, too. So it does help in certain ways, although it’s not a great way to have to learn the lesson. It is what we have, so you have to make lemonade out of lemon s, and I think that’s what all of us here have been doing.

Esther Schorr:
Thank you. And Jeff B?

Jeff Brochstein:
When I was first diagnosed, there were a handful of people, friends and family, who I told. And I can honestly say and somewhat brutally say this, there were some people that swept it under the rug because it’s a chronic condition. I didn’t need treatment right away. Many of them didn’t understand that, it being cancer, because they’re used to acute cancers, tumor‑based cancers that you have to attack immediately.

You know, I had other people who kind of buried me already because I told them cancer, and they stopped reaching out to me. And even up until today I still get a rare text message from some of these folks asking me, not in these words, but they pretty much ask me if I’m still alive. And I’ve kind of put them out of my life.

And there were some who were understanding, who actually read up on the things that I had sent them about CLL and how it’s chronic and how there’s all these emerging therapies on it.

So really for about a couple years after that, to kind of going to what Michelle was saying I was kind of in the closet about it. And then when my lymph nodes in my neck became a little more apparent and I really couldn’t explain it away all that easy, I came out a little bit more about it. And, you know, like I said, there have been people who have been very understanding. There have been people who have told me, well, it’s chronic and you’re taking a pill for it now so it can’t be that bad. And there’s been other people who have been like, oh, my god, cancer, you’re still alive. And, you know.

Esther Schorr:
I’m going to go a little bit out on a limb, Jeff. If I understood correctly you were diagnosed‑‑weren’t you diagnosed when you were still dating your wife? Is that?

Jeff Brochstein:
Her and I had just gotten engaged. We got married last year. She’s actually expecting, by the way, late February.

Jeff Folloder:
Congratulations.

Esther Schorr:
Congratulations.

Jeff Brochstein:
We’re having a boy.

Esther Schorr:
Oh, that’s so exciting.

Jeff Brochstein:
Thank you.

Esther Schorr:
And I bring that up because the other question I kind of wanted to explore with all of you is how did your diagnosis, if you’re willing to share, impact your relationship with your significant other or your spouse, you know, the person that’s closest to you? Was that different than dealing with other people? Anybody want to…

Jeff Brochstein:
I can start that off. You guys met Olga at ASH last year. If anything it’s solidified us. She’s a fire brand about it. She’s my rock. I really couldn’t make it through this without her. She’s been vital in terms of just my survival and us just having a happy life together. And we’ve been challenged by a lot of things. This is probably one of the biggest challenges, and it’s just made us better. So even under those circumstances, so.

Andrew Schorr:
Esther, I think I should jump in.

Esther Schorr:
Go ahead.

Andrew Schorr:
And you can tell us. So, you know, I was sort of more clinical. What do I have? What do we do, etc.? And as I said earlier, I thought my life was over, was relieved to find out it wasn’t. But all this was coming down on you too, and I don’t know to what extent you really shared how you were feeling because it definitely affects. We were‑‑you were a young woman. Esther’s seven years younger than I am, so you were younger. We had the idea‑‑we had two little kids, and we had the dream of having a third, so you might share what you were thinking.

Esther Schorr:
Sure. There was never‑‑I think the hardest person to share your diagnosis with was you, and my feelings about your diagnosis, the hardest one was to share that with you. And what was most helpful to me because I had loads of fears was to share it with other people who loved you as much, loved you in their own way as much as I loved you as my spouse.

So, you know, I think if anything it just solidified my dedication to our relationship and to figuring out the best way to support you emotionally and physically and professionally. So, yeah, you know, all of you have been talking about sort of there’s this weird silver lining of having a diagnosis of something. The silver lining is you look at what you’re really grateful for. And that’s really what it did for me as a care partner to you, Andrew. To say, okay, this ain’t good, but what’s the good stuff that we can do if we work together, and that’s really what’s happened.

Andrew Schorr:
We should mention that we began couples therapy.

Esther Schorr:
That’s right. We did, and that was very, very helpful so that I was able to communicate with you openly and you weren’t afraid to tell me when you had feelings, whether they were of fear or trepidation or not knowing how I was going to react. It took a long time for us to figure that out. I think we have.

Jeff Folloder:
One of the interesting things that happened in my particular journey, I got the diagnosis and of course everyone’s freaking out in the house. My wife is freaking out in the house, and she was being somewhat stoic about it and really didn’t know quite how to deal with things.

When the first doctor that I had seen that had given me the diagnosis described the treatment plan he wanted to do, I did a typical type A personality thing and said stop, went and talked with Dr. Google for an awful long time and decided that I needed a second opinion right then and there. And one of the watershed moments of my treatment journey was when we were sitting in that clinic room at MD Anderson when my doctor, not me, but to my wife walked over, picked her up out of the chair and gave her a bear hug to let her know that she’s a part of this process as well. It’s not just about me. And that was sort of a little bit of a release from the pressure valve because this is very much a team journey. I can’t even begin to imagine someone with CLL going through it by themselves, so I am extremely grateful to my beautiful bride of 31 years, and I could not have gotten to this day without her, period.

Esther Schorr:
Thank you. Michelle, did you have something you wanted to add on this?

Michele Nadeem-Baker:
Yes. A few things in that we waited until recently for couples therapy. I would suggest that it be started sooner, as you and Andrew did, because it would have been very, very helpful.

In the beginning I tried to protect my husband from things, and as I was living in Florida and he was in Massachusetts I considered not even telling him. In the first 24 hours, you know, your mind does crazy things. He was not with me because I didn’t even know there was anything wrong with me when I was told, and I even considered for him ending the marriage because it wasn’t fair to him. This all went through‑‑crazy things go through your mind. So I didn’t think it was fair to him, and his first wife had cancer. So the mind goes to crazy places.

Thankfully I did not. I shared, and he has been‑‑he has been by my side every step of the way probably much to his own physical health detriment, which is on track now. But he sacrificed a lot. He has been with me for every appointment. Every treatment he was by my side, every bone marrow biopsy. And thanks to him they redid some of mi tests which showed my genetic markers which they were not aware of as to how serious my CLL was.

He had read about that things could mutate or that tests only test a certain percentage of your blood and that perhaps it was different, and my symptoms were becoming more apparent that I was getting closer to treatment even though other things, other numbers did not show that through my FISH tests, my flow cytometry test. So he pushed them to redo the tests, and lo and behold, I was 11q, and they didn’t realize that. And IGHV they had known unmutated, but they didn’t realize the 11q. So I do suggest that people if they start seeing certain symptoms they do push for certain things, but my husband did that. I didn’t. I would not have pushed for that myself, so thank goodness I had a partner along the way, and I don’t think I could have done everything I did to be here today.

Esther Schorr:
If I’m reading all of you correctly, the relationship with someone else, a care partner, a caregiver, was additive for you.

Jeff Folloder:
Absolutely.

Jeff Brochstein:
Absolutely.

Esther Schorr:
And open communication.

Michele Nadeem-Baker:
Absolutely.

Esther Schorr:
Yeah. Because I know that we, Andrew and I, have spoken with patients where they really were reticent to share with the people closest to them for fear of scaring them, scaring them away, not knowing how they were going to react, so that’s a really important point.

The other thing I wanted to ask you all about was a few of you referenced having a wonderful medical team and finding a specialist and educating yourself. So finding the right doctor, educating yourself about the disease, what did that do for you? I mean, did it help you with just the emotional part of it? Did it help you feel more in control? Why was that a good thing?

Andrew Schorr:
Could I start, Esther?

Esther Schorr:
Yes.

Andrew Schorr:
So, first of all, Jeff Folloder mentioned about the doctor giving a hug and maybe it was probably Dr. Keating, but other doctors, Dr. Kipps down in San Diego gives hugs too.

I was‑‑put my hand out, and he said, no, I want to give you a hug, and he’s done that with you too, as Dr. Keating has. What it did by getting the right doctor is I think gave me, and I think you too, confidence. And this ties in to Jeff Brochstein as well. Confidence to go on with your life and at that age, earlier age, said go ahead and father a child, which is a big deal, right? That’s not just a short‑term thing. And I’d be interested in what Jeff Brochstein says, but I know you and I, Dr. Keating gave a hug and said, go have your baby, which here we were in a major cancer center. Go have your baby.

Esther Schorr:
And he’s 21 now.

Andrew Schorr:
Yeah, he’s 21 and he drives us crazy and we love him, but he’s our thirties, he’s our miracle baby. And, Jeff, you and Olga having the confidence to do that.

Jeff Brochstein:
Well, Andrew, a couple, I mean, we’d been trying for a while, and a couple of years ago a doctor told Olga and I that we had a better, almost a better shot of hitting the Powerball than we did of conceiving, and it kind of happened on its own a few months ago.

Esther Schorr:
That’s great.

Jeff Brochstein:
So it’s really a miracle. You know, I think what really found a comfortable place for me is I found a community oncologist who did have a specialty in hematology though he wasn’t a research specialist who has a great bedside manner, and he was also very cool with me going to MD Anderson and talking to Dr. Thompson and talking to a research specialist, and that gave me a good counterbalance. That gave me that second opinion. I could weigh that with what Dr. Stephen Szabo here at Emory was recommending, and I came up with what was best for me.

And Olga‑‑and us getting pregnant was just all the more of a present on top of that, so life is good in that regard.

Esther Schorr:
Any other comments on that? Jeff?

Jeff Folloder:
I’d like to chime in just a little bit. Andrew had mentioned Dr. Keating and his bear hugs and all that wonderful you stuff. One of our very first appointments with Dr. Keating, I felt the need, as many new patients do, to sort of like unload the guilt, all the things that I was doing that may or may not be exactly healthy, so it was sort of like a confessional.

And I can remember telling Dr. Keating, okay, you need to know that I smoke an occasional cigar, maybe an occasional briar pipe. And he asked me, well, how often do you smoke, and I said, ah, three or four times a month. And he said, okay. And I didn’t quite understand what okay meant. And then I kind of confessed, okay, you need to understand that most evenings I have a whiskey or two.

And he asked me what type of whiskey I drank, and he complimented me on my taste. And he actually stopped me and said, I am here to help you live a good life, not make you miserable. That’s where we were focused on. My first doctor just wanted to start treatment. Dr. Keating wanted me to live well, so instead of just getting a, quote/unquote, gold standard of treatment, Dr. Keating was focused on getting me the best treatment. So that was sort of my start to living well.

Esther Schorr:
Yeah. That’s how we felt about finding the right team for you, Andrew, was that. It’s what’s the quality of life and what are your priorities in your life and will your medical team‑‑is that what they’re focused on.

Andrew Schorr:
Right. You know, I make one comment about that, Esther, and I want to hear what Michelle says too.

So we’re blessed now with a range of‑‑a whole array of treatments, Jeff, you recently, Jeff Folloder led a town meeting in Jeff Brochstein’s home town recently where you spoke about that, that there are more treatments either approved or in research than ever before. So part of it is what’s your situation, and Michelle talked about unmutated and 11q, what treatment lines up with that clinically, but also what are your goals? Somebody who has FCR might be able to stop treatment after six months if it’s right for them and if it works for them. Some people may‑‑there’s some idea with Venclexta combined with Gazyva, maybe you’ll be able to stop after two years. With ibrutinib you’re taking it long term.

So what’s right for you? And I think all of us need to take a look at our lives, have a conversation with a knowledgeable doctor and state our goals. What are our personal goals for what works for us. Michelle, I mean, you may have things you want to add too.

Michele Nadeem-Baker:
Certainly. So when I went on the clinical trial I’m on, which some people know as IFCR, ibrutinib and FCR, I did not know at the time nor do I think they knew long‑term what would happen, but here it is. I can’t believe it. It’s three years this month I’ve been on it. I’ve been on ibrutinib for three years now, and I will be indefinitely until either it stops working or something better comes along, and I am able to live life. I am looking of course, as we all are, for a cure someday, and I’m still not MRD negative. That would be wonderful. That would be great. But right now I’m holding steady, and that’s a good thing. So my goal is to be able to live life as healthy as I can, and that’s what this is doing right now.

Esther Schorr:
Great. Well, so, I’m going to switch gears a little bit, and I want to ask you all a question. Have any of you dealt with a situation where you tell somebody what’s going on for you and they say, well, you don’t look sick. What do you say? What do you do when somebody says that to you?

Jeff Folloder:
A lot of smiling and nodding. It is a very common response. I think the two most common responses that we as CLL patients hear is, one, you don’t look sick, or two, oh, you’ve got the good cancer. Neither of these are acceptable. Yeah, I look good because I work at it. The whole concept of you don’t look sick, well, there’s a difference between looking sick and feeling sick, and as a CLL patient I take as much charge of my physical well‑being as possible. Before I was diagnosed with cancer I was a couch potato. I never exercised.

I didn’t need to. I was pretty lethargic and sedentary. Now I’m an avid power walker knocking out between 30 and 35 miles every week. I do it pretty fast, too. I’m trying to maintain my weight, and I’m trying to maintain my energy level. So, no, I don’t look sick. Sometimes I feel sick. I just did a week and a half on the road. I missed a bunch of naps. I’m a little tired. Actually, I’m a lot tired, and I’m looking forward to a nap this afternoon. And I’m going to take one, and it’s okay.

But this is part of my new normal. My new normal is the way I feel doesn’t necessarily show. And my wife understands that. My family understands that. The people close to me understand that. My doctors understand that. So if people don’t get it, that’s their problem, not mine.

Esther Schorr:
Any other commentary on that? I think that’s a great, very positive way of looking at it.

Michele Nadeem-Baker:
I have to say that I’m trying to look at the positives about people saying you don’t look like you have cancer. In other words, I feel like they’re trying to convince me I don’t have it because I don’t look it, but I guess I’d rather not look it than look it. That’s what I keep trying to tell myself. And as Jeff just said, I do smile a lot, it’s like, oh, yeah, you really don’t know what you’re talking about, but thank you. I know you mean it to be good and be nice. I also know people don’t know what to say. So I try to put the little sarcastic bubble aside and just try to think of that.

But as Jeff said you do have to‑‑you have to take charge. And I continue to, as Jeff was saying, I continue to work out in the way I do throughout even infusion. Continue to go to the gym and use weights and do cardio. And when the weather’s good enough up here, which it’s now turning to not be, do whatever I can outside as well as in the gym because you feel better.

And that is one way I felt I could take control when everything else was out of control health‑wise. So it also helped me in that way, in that respect as well as to be healthier physically. So it’s very important, I’d say.

Esther Schorr:
And really what you guys are all talking about is how do you stay empowered and positive. And for you, Jeff, it’s everything from power walking to taking naps, and for you, Michelle, it’s going to the gym and being an advocate. And Jeff, Jeff other Jeff, you’ve talked about some of the things that you do. And you’re going to be a lot busier with a baby in the house.

Jeff Brochstein:
That’s right.

Esther Schorr:
Anything else that helps you to stay positive in all of this?

Jeff Brochstein:
You know, I was always active for I don’t know 20 years before I was diagnosed. I’ve always lifted weights, done Cross Fit in recent years. So I spoke about this earlier, and this really kind of repeats some of the stuff that Michelle and Jeff were saying.

I’ve never appeared sick. I’ve always been physically fit. There was a time for about two years since I was diagnosed that I had some lymph nodes that went away once I started the ibrutinib. People never associated me with some sort of chronic or acute illness. And when I’ve told them what I have and I’ve told them about the condition, you know, I’ve also followed up with just trying to create awareness around this, send them some links, sending them some videos. Maybe sending them the original video I did at ASH last year, just to really create awareness around it. And it’s really up to them if they want to absorb it, on Jeff’s point.

Esther Schorr:
So, you know, I think to kind of wrap up all the things we’ve talked about, what advice do each of you have that might help someone who is facing a diagnosis of CLL in midlife? What lessons have you learned along the way that helped you face it?

You know, just kind of giving somebody advice, what would that advice be? And maybe, Andrew, do you want to start?

Andrew Schorr:
Yeah. I will say first given what we know about CLL and the range of things going on how, your life is not over. I thought my life was over. Here we are. I was diagnosed in 1996, or 22 years. I mean, I had no idea that I’d make it 22 months, right? And if you read some of the old articles and stuff you’d say, oh, life expectancy is not very long. So first of all, you’re going to live a long life and thank god for the medical research and the array of things that are available.

And I think Michelle said it too, right now, she’s been in a trial, she continues to take the ibrutinib, maybe there’ll be something else that she’ll need at some time and we’re confident that there will be. So, Esther, you remember that there was a guiding light, a patient advocate in CLL years ago when I was diagnosed, and she gave us two words as advice.

Chill out. And so that’s what I’d say. I’d say chill out. I don’t mean to be harsh. There’s a lot of grieving that goes with a diagnosis. I’ve probably said it to my friend Jeff Brochstein when we met in Atlanta last year, to you and Olga, but I would say that, and that’s based on evidence. That I’m living longer and people living a long time. And we get an eye into the research going on, and there’s a lot. So I think‑‑it’s not perfect. There are side effects, there are expenses, and there are course corrections in your head as well as in your life, but you’re going to live a long time. Believe me.

Esther Schorr:
Nice. Jeff B, any advice you would give to someone?

Jeff Brochstein:
Really along the same lines that Andrew just spoke and what Jeff had mentioned when he gave his intro. When you get CLL, when you get a diagnosis of this kind, god forbid, but when it happens during these years just take the what‑ifs out of your life. Take the projection out of your life because that will just make you grow worrisome and grow older and grow grayer. You really have to‑‑just to take things by the day. Just do your best early on to do as much research as you can about it. Try to see a specialist early on. I think that would helped me out my first couple of years if I would have gone to see a specialist as well as have somebody local and community‑based where I lived.

Reach out to people like Andrew, to groups like Patient Power. It’s a different world now than it was 10 years ago in terms of technology and information that’s out there. And I think most of all just keep tabs on the treatment landscape that’s changing every month it seems like or every six months something is approved, something new, something better, something not chemo related. Really, just pay attention to those things and you’ll be okay.

Esther Schorr:
Thank you. Jeff?

Jeff Folloder:
I would tell everyone that is recently diagnosed with CLL to do a couple of things. First, take a deep breath. I guess during pregnancy they would call that the cleansing breath, but you’re going to need to do a couple of them. So remember, that, Jeff, cleansing breaths.

Second, everyone has said it again and again and again. See a CLL specialist. You don’t have to see the specialist regularly, but you need to get a CLL specialist as part of your team. The landscape of medicine is changing not just monthly. It’s changing weekly, daily and hourly. One of the things my doctors keep on telling me the longer we wait the more likely we come up with something even better to treat you with. When I was first diagnosed we never heard the word “cure.” Now we’re hearing the word “cure” for some forms of CLL, and it’s getting better for lots of people very, very fast.

Make a few goals. I want to do this. I want to do that. Esther, you guys just saw Bruno Mars. Well, you saw him in a coffee shop. I’m going to go see him in concert this weekend. Why not? This is not a death sentence. This is just a part of my life. So I’m going to go do the things that I want to do, and that’s what I tell every single patient. At several of our town meetings I have made the point to remind people that statistics only look backwards. When you start looking at Dr. Google you’re going to see that the average life expectancy of a CLL patient is about six years. Well, that’s only looking backwards. I’m now nine years into it, so some people would say that I’m past my expiration date. I don’t look at that way. I’m living a great life. Every minute that I’m kicking, I’m kicking it for real.

Esther Schorr:
Thank you, Jeff. And, Michelle, any parting advice in this discussion?

Michele Nadeem-Baker:
That’s a tough act to follow.

Michele Nadeem-Baker:
So I would say the number one thing is to educate yourself and not just with as Jeff calls it, Dr. Google. Because if so you will get frightened by what it says because it does look backwards. But I would say to educate yourself as much as you can through credible sources, through current information versus past. Otherwise, you’ll get really frightened.

And the other thing is for those of you watching this, Patient Power generally has the leading doctors around the world for CLL on it. If you can get to one of those doctors that you see or one of the institutes, then that is a great source to go to to find out what is best for you to match you up.

If you do need treatment yet or not, projected time to treatment. And then if you can either go to whichever doctor that is, or in conjunction to what Jeff of Atlanta as opposed to Jeff of Texas is doing, pair that with your community doctor if at all possible so that you don’t have to travel. But that way you can be confident that you’re getting either in a clinical trial tomorrow’s treatment today or the best in treatment there is today. And there are so many out there.

The other advice I’d give, and someone gave this to me in my first week of diagnosis. Stay as healthy as you can today because there will be something to treat you tomorrow. And we’re all proof of that, all of us here right now.

Jeff Folloder:
Excellent advice.

Esther Schorr:
Yeah. Those are all such great advice, and you all are a delight and an inspiration to talk to. I feel very honored to be sort of in the middle of this circle of empowerment.

I want to thank all of you, Michelle, the two Jeffs and Andrew, for sharing your personal experiences as positive and very empowered CLL patients. It’s always inspiring to talk with each of you, and you provided some great perspectives and suggestions. And I want to thank our CLL community for joining us today and I hope that this conversation has been helpful to you. I’m Esther Schorr. Thanks again.

Ask the CLL Expert – Dr. Jeff Sharman

Ask the CLL Expert – Dr. Sharman

 

“Ask the Expert” session with CLL specialist Dr. Jeff Sharman from Willamette Valley Cancer Institute and Research Center.


Transcript:

Recorded on: September 27, 2018

Andrew Schorr:
Greetings to this live Ask the Expert program for those of us dealing with CLL. I’m Andrew Schorr from Patient Power. Welcome to this Patient Empowerment Network program with financial support from AbbVie and Pharmacyclics. Thank you so much for being with us.

We have a wonderful expert with us today who is so knowledgeable about this, and that is Dr. Jeff Sharman. Dr. Sharman is the medical oncologist, of course, one of them at the Willamette Valley Cancer Institute and Research Center in Oregon. He’s also the medical director for hematology research at the US Oncology Network with oncologists all across the country. Jeff, welcome back to our program.

Dr. Sharman:
Thank you so much. It’s nice to be here today.

Andrew Schorr:
Okay. Let’s get started. We have a lot of questions coming in, and if you, our viewer, have an additional question send it to cll@patientpower.info and we’ll cover as much as we can in the next half hour.

Here’s a question that came in based on news events that people follow related to CLL, and this is from William. He says, I heard there’s a new drug approved for CLL, duvelisib. Can you tell more about this? Where does it fit in in the CLL landscape?

Dr. Sharman:
Absolutely. Duvelisib is another PI3 inhibitor. It has considerable molecular similarity to idelalisib, which was the first in class medication approved amongst the PI3 inhibitors a few years ago. This molecule has considerable both biochemical similarity, structural similarity but also quite a bit of clinical similarity. So when you look at the patient population in which it’s approved, similar clinical trial designs led to approval, and so as a result it’s sort of in the third‑line setting that you could use it.

It is a‑‑the drug class is a sort of the whole PI3 family of which there’s a growing number. There’s idelalisib, umbralisib is in late‑stage clinical trials. Copanlisib is approved in follicular lymphoma but not CLL. And as a family they tend to be utilized less frequently than the BTK inhibitors such as ibrutinib and to some degree less frequently than venetoclax, as well, the Bcl‑2 family, and that has to do with some of the side effects, that there is, a frequency of diarrhea, LFT abnormalities and so forth. So it follows on the heels of idelalisib, and I would say has more similarities than differences.

Andrew Schorr:
Okay. Let’s go on. You mention about side effects. People ask about that all the time, so here’s a question from Judy. She says, I’m not able to get an answer from my husband’s oncologist regarding ibrutinib and severe body cramping. Have there been any reports showing this is a possible side effect from ibrutinib?

Dr. Sharman:
Absolutely, it is. It is‑‑well, absolutely possible, let’s say that. It actually is what I would say one of the most common side effects that I encounter as a limitation for ibrutinib. The medical term for it is arthralgias, which is sort of translates into joint pains. Sometimes you’ll also see actual cramps or spasms. I’ve had patients’ hands lock up when they’re driving sometimes, which can be a little bit concerning.

There is I think considerable question in the field. There are differences amongst thought leaders on this as to whether‑‑how to best manage it.

There’s some studies that suggest that lower dosages may‑‑after a patient has been on ibrutinib for a length of time you may be able to get away with lower dosages. Those pieces of clinical trial data are not as large and not as well validated, so I think it’s still in the hypothesis‑generating mode, but there’s some data that suggest you could do it. And if the choice was lower dose of ibrutinib or no dose of ibrutinib, I would probably go with a lower dose.

The other potential solution now is acalabrutinib, which is a second BTK inhibitor approved. It is approved by the FDA for mantle cell lymphoma. However, a lot of the clinical trials are in chronic lymphocytic leukemia, and there have been studies that looked at patients who have limited tolerance of ibrutinib, and in many cases they were able to go on acalabrutinib without a recurrence of the same side effects.

So that’s another possibility. It is in the NCCN guidelines that for those patients who have intolerance of ibrutinib consider acalabrutinib. So whether it’s dose reduction or drug substitution, those are sometimes two ways that I use to get around that scenario.

Andrew Schorr:
Okay. Now, we should be clear that acalabrutinib is not yet approved for CLL. Does it seem like that’s forthcoming? I mean, nobody can guess the FDA, but.

Dr. Sharman:
Yeah. So the clinical trial that will lead to approval, presumptive approval, was a head‑to‑head comparison against investigators’ choice of bendamustine rituximab or idelalisib rituximab, and that study is fully accrued and waiting for end points.

And I think that the feeling would be that should be a positive test and that it would eventually get CLL approval. Most of the studies have been done in CLL. It’s just the mantle cell indication came along more quickly.

Andrew Schorr:
Okay. All right. A lot of people worry about other side effects like fatigue, of course, in CLL. So here’s a question from Patty. She says, I’ve been taking 60 milligrams of Vyvanse, which is often used for ADHD, for extreme fatigue that she struggles with. And she says her blood pressure is elevated, and she’s read that that can be a side effect of Vyvanse. Are there any new or additional medications that can be used to treat fatigue without the worry of high blood pressure?

Dr. Sharman:
The way I would approach that situation, fatigue‑‑what I don’t know about this particular patient, is this fatigue that is attributable to the CLL or fatigue that’s attributable to medications?

CLL fatigue is probably one of the most bothersome sort of clinical realities, and for some patients even though they may not meet other treatment criteria such as rapid rise in white blood cell counts, systematic (?) inaudible adenopathy, marrow dysfunction. Sometimes fatigue is so debilitating that you need to do treatment for it. In the 2008 guidelines, fatigue was one of the‑‑it was like the sixth indication for when you treat CLL.

And I’ve seen some patients, you know, one immediately jumps to my mind. He’s clinician himself, very busy individual, likes to surf and so on and so forth, but his CLL left him so fatigued that he had to cut back on clinical work and so forth. And getting his CLL under control really made a huge difference for him. So in the setting of CLL I think that you may wish to consider talking to your doctor about going ahead and treating.

I find those are difficult, difficult discussions because if you don’t have the more classic indications for therapy it’s hard to know. Because fatigue can be a number of things. It can be thyroid dysfunction. It can be hormone imbalance with other hormones. It can be nutrient deficiencies and so forth.

Andrew Schorr:
It could be having three kids.

Dr. Sharman:
Absolutely.

Andrew Schorr:
Yeah, I know. Lots of things.

Here’s another question from Bob. Bob wants to know, will approaches likely change for first‑line treatment, for instance venetoclax, or Venclexta, within the next two years? You have ibrutinib first line.

Dr. Sharman:
Yeah.

Andrew Schorr:
You have FCR that’s been around. You have idelalisib I think could be used first line.

Dr. Sharman:
Actually, idelalisib is specifically contraindicated for first‑line therapy because of side effects.

Andrew Schorr:
Okay. So what about first‑line therapies, Jeff? Where are we there and what’s coming?

Dr. Sharman:
Yeah, so you’re kind of in this bind currently where your choices are chemoimmunotherapy or targeted therapy, and both of them have strengths and weaknesses. The strength of chemoimmun0therapy is that you give treatment for a fixed duration of time, and then you get treatment‑free interval that in properly selected patients should be measured in multiple years.

Andrew Schorr:
I went 17 years.

Dr. Sharman:
Yeah, absolutely. So effective therapy in appropriately selected patients. Now, when I say appropriately selected patients, that does get into some of the nuance about FISH changes and IGHV mutation, and I will tell you even amongst thought leaders in the field there’s some debate as to where you draw the line. Some patients are more suitable for ibrutinib either because of co‑morbidities or wish to avoid chemotherapy, but at least as of today ibrutinib is something you start and then stay on indefinitely.

And per the prior question, some patients have difficulties with that, whether it’s arthralgias or bruising bleeding and so forth. The medication you made mention of I think is the frontline therapy that may have the most profound impact on treatment selection in the next two years.

Andrew Schorr:
Venetoclax.

Dr. Sharman:
So the German Research Group, which is really just absolutely one of the best out there, have fully enrolled a clinical trial of obinutuzumab venetoclax versus chlorambucil and obinutuzumab, and I have to believe that that is going to result in a superior outcome for the venetoclax arm and that we will have the combination of obinutuzumab venetoclax for front‑line setting.

And what’s really appealing about that is that is one year of treatment and then treatment is suspended and stopped. And though we haven’t compared that to more traditional BR or FCR, I think it would be a highly effective regimen. We are currently conducting a study in the United States in our research network looking at the combination of obinutuzumab and venetoclax, and what I like about our study is we give‑‑for the listeners who might not be familiar with venetoclax, starting venetoclax is a little bit clunky because it works so quickly we have to be careful about a condition called tumor lysis syndrome, which is if you kill too much cancer cells too quickly that can cause some dangerous conditions, and venetoclax does do that.

And so what we’re doing is we’re giving two months of obinutuzumab and sort of getting rid of the bulk of the CLL and then starting the venetoclax hopefully under much safer conditions because, you know, in the Pacific Northwest we would say you can’t have forest fires if you don’t have any trees. So if we get rid of all the CLL or a substantial fraction of it somebody is less likely to have tumor lysis. So I think that’s the approach that is probably the next up in frontline.

The one other thing that could potentially change is acalabrutinib has conducted a three‑arm study‑‑excuse me, Acerta with acalabrutinib, where they give‑‑it’s a three‑arm study with either chlorambucil Gazyva, acalabrutinib or acalabrutinib with Gazyva. And so does the addition of a C‑20 antibody make BTK work better, remains the question outstanding.

Andrew Schorr:
All right. Let me just explain things to people. I’ve been around this for a long time and Jeff deals with these acronyms all the time. So, first of all, Gazyva is the same as obinutuzumab.

Dr. Sharman:
Thank you, yes.

Andrew Schorr:
It’s an infused CD20 that’s targeting the CD protein on the B‑cell, the bad guy, and it is sort of I don’t know if you’d describe it as a more powerful version but it followed from Rituxan or rituximab that many of us had. So the idea is you have an infused therapy for some length of time, and then you may have an acalabrutinib with it or you may have a venetoclax or Venclexta with it. Get I get it right, Jeff?

Dr. Sharman:
Yes. And if I just had one other comment. I think there are a lost questions and certainly some very compelling data about the combination of a BTK inhibitor such as ibrutinib with a Bcl‑2 inhibitor such as venetoclax.

Andrew Schorr:
Two pills.

Dr. Sharman:
Two pills, yes. And I think the preliminary data really looks extremely encouraging.

The challenge with that approach is it’s not approved in that combination and probably not going to be approved in the next two years unless the FDA does something that maybe I’m not anticipating at this point. That clinical trial that compares that to an existing standard is really only just getting off the ground now.

Andrew Schorr:
Okay. All right. Let’s buzz through some others. So John writes in, please compare purpose and benefit differences for FISH testing versus next generation sequencing. So maybe you could explain them too.

Dr. Sharman:
Absolutely. Thank you for the question. It’s one that I think is often very difficult to comprehend.

So a little bit of history here is that we’ve known for a long time with that patients with chronic lymphocytic leukemia have a pattern of common chromosome gains or losses, and we generally pay attention mostly to five separate categories.

There are some others that people sometimes look at, but ranging from sort of worst to best, worst is having a loss of chromosome 17p and P stands for petite arm, so part of the short arm of chromosome 17 is lost. 11q, Q stands for the long arm of chromosome 11. And then you have normal chromosomes or the addition of an extra chromosome 12 or the loss of a portion of chromosome 13 that kind of goes from worst to best. And that is very different than actual mutations in genes. So these are wholesale losses of large clunks of chromosomes.

And if you look at 17p the reason that 17p is bad is because there’s a particular gene there that’s very important called TP53, and you can actually have a mutation in TP53 without the presence of a chromosome loss. And so next generation sequencing looks at a host of additional genes that really until the last three to four years we didn’t know have the significance that they have. So TP53 is probably the most important, but you’re also seeing things such as SF3B1, NOTCH1, FA1. There are a variety of them that are out there. Some are better understood than others, and I think to some degree we’re still as a field even trying to figure out how best to integrate these into our clinical practice.

Andrew Schorr:
Okay. So would you recommend for the typical CLL patient that they have FISH testing, which tells you about the chromosomes, right?

Dr. Sharman:
Yeah.

Andrew Schorr:
And when do we need to do genomic testing to see with whether if any of those genes you just rattled off?

Dr. Sharman:
Yeah. So I can tell you about my own personal practice on that. I do think that the field, as I indicated before, is still trying to digest this, and a number of those specific mutations there isn’t necessarily super robust consensus as to when is the best time to draw those. So I’ll explain how I’ve thought through it, and if that resonates with you.

So my question in the previously untreated patient is whether or not this patient is suitable for chemoimmunotherapy. Previously I said appropriately selected patients get very long duration responses. I don’t want to give chemoimmunotherapy to a patient who is not going to get a sustained benefit.

If I anticipate that I’m only going to get 18 months benefit or two years of benefit, it is not worthwhile in my mind going through the chemotherapy to get that. I would rather put those patients on a tyrosine kinase inhibitor.

So my first stratification is the IGHV mutation status, and I would say in general if somebody’s mutated, which is the more favorable form, I would tend to err more on the side of chemoimmunotherapy for those patients. For those who are unmutated, which is the bad one, I would tend more towards targeted therapy. These aren’t totally black and white.

But my next level of stratification is FISH. So if you’ve got a bad FISH finding even if you’re in that favorable category I strip you out from the chemotherapy group.

Andrew Schorr:
So like if you had a 17p deletion, those chromosome deletions?

Dr. Sharman:
Yes. So if you’re mutated, which you think is good, but you also have a 17p, then I wouldn’t give that individual chemoimmunotherapy.

So if you have good IGHV, good FISH, good functional status and I’m thinking about give you FCR, that’s my final check is let’s make sure there’s not something lingering underneath the surface here that I don’t know about. So that’s where I check it.

Now, in the relapsed/refractory setting it is more the norm that those patients are almost all going on novel agents where those mutations are sort of a little bit less salient, so I don’t necessarily check that. However, I do recheck FISH with successive lines of therapy because that certainly can evolve. And to make things even a little bit worse now for somebody who has been on BTK, we need to think about BTK mutations and whether or not that patient might be suitable for a second‑ or third‑generation BTK inhibitor that can get around that.

Andrew Schorr:
Okay. And the genomic testing, when do you do that?

Dr. Sharman:
Well, so genomic testing is looking for those smaller mutations that don’t show up on FISH.

Andrew Schorr:
Okay.

Dr. Sharman:
So that’s my final break point before I would give somebody chemoimmunotherapy. But I will tell you, there are opinion leaders out there who will argue that chemoimmunotherapy is dead and shouldn’t do it.

Andrew Schorr:
Right. There are.

Dr. Sharman:
I’m in the camp that thinks there’s still purpose and value in doing that in appropriately selected patients.

Andrew Schorr:
Okay. Let’s get to some others. So Grant said he was diagnosed with a double diagnosis of diabetes and then, as he had additional testing, voila, he also had CLL. So he’s currently able to control his diabetes, and he’s in watch and wait for CLL. Is there any advice for me going forward with these two conditions? Diabetes and CLL.

Dr. Sharman:
It‑‑so I guess my question in such a circumstance is how is that CLL behaving. If he has a molecularly favorable CLL and he’s on watch and wait and things are simmering along, it may very well be that his diabetes poses a greater threat to his overall health than the CLL.

In contrast, somebody with an unmutated 17p deleted CLL, it’s the CLL that’s going to be more dangerous. Fortunately, the treatment interactions don’t overlap all that much. Sometimes with chemoimmunotherapy we give steroids, and that can be problematic for patients with diabetes, but I would manage them by and large independently.

Andrew Schorr:
Okay. We’ve gotten several other questions. Sharon, we got yours and Jason. They were asking about first line with ibrutinib, and I think we spoke about that and other choices that may have a different side effect profile if ibrutinib has a problem. And also Sharon had written in about she’s in this watch and wait and she wonders about FCR, and I think we can hear from you that FCR and maybe BR in some cases, which is this chemoimmunotherapy approach, still has a place in your mind. So, Sharon, stay tuned.

Lucy wrote in. She says, given the 17 (?) (p53) deletion what role does that play in determining the beginning of treatment for the CLL naive patient, and you were just saying probably not FCR or BR.

Dr. Sharman:
Yeah. Boy if somebody had a 17p deletion I would strongly advise against traditional chemoimmunotherapy. I think it can actually be more harm than good in some cases.

There is a more subtle point though that I would jump onto, which is what factor does it play in first‑line therapy. It’s not so much the agent. Some people feel like because they’ve got a 17p they need to jump into treatment sooner rather than later.

I will tell you I have several patients with 17p deleted CLL that I’ve been able to watch for years and years and years without treatment. The indications for starting therapy really remain the same. If I see somebody clearly heading towards treatment with a 17p I may start them a little bit earlier, but again some of these folks can be watched and wait quite well.

Andrew Schorr:
Okay. You’re a director of research, and we’re starting to hear about CRISPR or gene editing.

Dr. Sharman:
Yeah.

Andrew Schorr:
So do you think this gene editing will play a role in CLL?

Dr. Sharman:
Hoo, boy. You know, I think that probably dovetails with the question you didn’t ask, which is about CAR‑T cells. I think CRISPR, for members of the audience who may not be familiar with it, is a highly efficient, highly directed way of making genetic manipulation within cells,

and with a lot of the gene therapy that’s been done over the years we sort of randomly insert genetic material into cells to sort of reprogram them. That’s sort of the classic way of doing gene therapy. The problem with that is there are parts inside the genome that don’t like to be broken, and so the field really was set back a number of years when there were some early cases of leukemia caused by gene therapy.

And so what CRISPR does is it does allow you to make very targeted genetic modifications so that you can precisely put in new genetic material sort of wherever you want it. And I think that in the context of CAR‑T therapy there’s now goals to make it much more off the shelf than this sort of highly manufactured thing, and that’s where I would see CRISPR having the most likely early role.

Andrew Schorr:
Okay. So CAR‑T, chimeric antigen receptor T‑cell therapy, taking a virus, I think, and combining it with stuff for your T‑cells, targeting your CLL. So Lynne just asked, she’s 71, would somebody older like that‑‑tomorrow is my 68th birthday, folks‑‑would we be candidates for CAR‑T should we need it?

Dr. Sharman:
Well, I need to articulate some of my limitations as a community practice oncologist, thus far the CAR‑T research has been sort of in the exclusive purview of academic centers, so I haven’t had the chance to do it yet. That having been said, we are working with a variety of sponsors to get such a program up and running.

However, I will say there’s a lot of enthusiasm in CLL because the original New England Journal of Medicine paper that described CAR‑T was done in both pediatric acute leukemia and adult chronic lymphocytic leukemia, and it is now approved by the FDA for the pediatric ALL, acute lymphoblastic leukemia. It is not approved for CLL. And part of that‑‑there’s a lot of reasons why it doesn’t work as well in CLL as it does in other diseases, and I think that the‑‑it’s okay that this is moving a little bit more slowly in the CLL field because I think we’re getting a lot of benefit of accumulating knowledge in how to make it work best in CLL. I think it will become an important therapy in CLL.

Keep in mind that the toxicity of chimeric T‑cell is significant, and the possibility of neurotoxicity or this syndrome that looks a little bit like sepsis that’s not sepsis but it looks like it in a lot of ways, what we call cytokine release syndrome make this a therapy where caution is advised.

And so if it’s something you’re thinking about I would say go get yourself seen in your very specific circumstances with somebody doing this in research studies and decide if it’s right for you.

Andrew Schorr:
Okay. And we’ll have‑‑in other programs we’ll talk about CAR NK research that’s going on. Lot to talk about, maybe at ASH, folks. Dr. Sharman will be at the American Society of Hematology meeting, the ASH meeting here in San Diego in a couple of months. We’ll have coverage from that as these new areas come out.

Now let’s go back to the basics before the end, Jeff, and this that is flu season coming up.

Dr. Sharman:
Yes.

Andrew Schorr:
And there’s also a shingles vaccine. And also some people related to hepatitis B.

What are you telling your patients about vaccines? My friend Jeff Folloder said somebody at MD Anderson had them maybe getting two flu shots.

Dr. Sharman:
Yeah.

Andrew Schorr:
So first of all, flu shots, and do we need more than one? And what about these other shots?

Dr. Sharman:
Yeah, so starting with flu I would encourage all my patients CLL patients to get flu shots. The response is nearly universal. Everybody always says, well, I got a flu shot and I still got sick. A flu shot does not prevent all illness. Flu prevents flu. And patients with CLL get more complications from flu because their immune system has a cancer in it. So CLL is a cancer of the immune system, so to whatever extent you can give yourself a head start to fight off flu I would encourage patients to do so.

Andrew Schorr:
More than one shot?

Dr. Sharman:
Well, so I will say that patients with CLL generally have less of a response to a flu vaccine than somebody without CLL.

So you don’t get as much protective benefit if you have CLL as somebody without it. I don’t think, at least, I’m not familiar with data that says two flu shots are better than one. It may be out there and I’m not aware of it, but I mean I could understand why you might. It at least biologically makes sense.

Andrew Schorr:
And the shingles vaccine?

Dr. Sharman:
Yeah, so very few clinic days go by where I don’t curse shingles at least once. For anybody who has had shingles you know it can hurt really badly, and there is this condition called post herpetic neuralgia, which is a sort of a lingering pain syndrome that can go on for years for patients who have had shingles and can be a life altering pain. And so, again, I think whatever head start you can give your immune system it’s worth doing.

And I guess the reason why I curse shingles so frequently is because it does seem to go part and parcel with lymphomas and CLL. Again, you have a cancer of the immune system. The immune system doesn’t work as well, and, boy, I can’t count the number of times where somebody gets shingles just as their CLL is acting up and then it delays treatment, or somebody is going through treatment with a lot of pain as a result.

Andrew Schorr:
So you’re not worried about the vaccine?

Dr. Sharman:
No. Not only am I not worried I highly encourage it. But I would point out that the old vaccine was a live virus, and there were problems giving that to patients with CLL. There is a new dead virus, Shingrix, that’s in short supply.

Andrew Schorr:
Okay. Well, we’re going to wrap up. I want to just help everybody understand what I alluded to a minute ago, the world series of blood cancer‑related discussions where a lot of data, and, Jeff, you may have data presented there, is the American Society of Hematology meeting which is near me in San Diego in December and about 30‑, 40,000 people come and discuss all this.

So stay tuned. We’ll be doing programs from there, and we’ll bring you updates. Dr. Jeff Sharman, thank you so much for being with us once again.

Dr. Sharman:
My pleasure, Andrew. Thank you for your time.

Andrew Schorr:
All right. And this is what we do. Thanks to the Patient Empowerment Network so devoted to this. We’re happy to help from Patient Power, and thanks to the supporters for this program. They had no editorial control, but they believe in education. That’s AbbVie Incorporated and also Pharmacyclics.

I’m Andrew Schorr. Remember, knowledge can be the best medicine of all.


Please remember the opinions expressed on Patient Empowerment Network are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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