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ASH 2018 – Latest News and Research in Multiple Myeloma

ASH 2018 – Latest News and Research in Multiple Myeloma from Patient Empowerment Network on Vimeo.

Dr. Amrita Krishnan, Director of the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, shares the latest news and research that was shared at the ASH 2018 conference in the field of Multiple Myeloma.


Transcript:

Esther Schorr:

Hello to everybody.  This is Esther Schorr with Patient Power, and I’m here today at the 2018 ASH conference, the American Society of Hematology.  And I’m surrounded by, oh, 20-, 25,000 amazing researchers and clinicians who are studying hematological malignancies.  And I have about me today Dr. Amrita Krishnan.  Is that correct?

Dr. Krishnan:
That’s correct.

Esther Schorr:
And she is the Director of the Multiple Myeloma Program at the City of Hope in Los Angeles.  Thank you for being here.  So what I wanted to talk to you about today is what’s going on for myeloma patients.  What are the headlines from ASH this year?

Dr. Krishnan:
Good morning, Esther.  Thank you for the opportunity to talk.  I don’t even know where to begin.  There’s—every myeloma session has been packed, standing room only, which tells you obviously, number one, the advances we’re making and the enthusiasm regarding them.

I’d say the three biggest news really is obviously CAR-T cells in relapsed disease, and we started out just hearing about one CAR-T construct, the BB121.  Now we obviously are hearing many other companies presenting their results and other CAR-T constructs, which I think is very good for us because we can understand better both the technology as well as side effects and efficacy and understanding among different T-cell constructs.

The other big thing, I would say, antibody drug conjugates by specific antibodies.  And then the last but not least let’s not forget in terms of stem cell transplantation there was a big session this morning looking at new drugs in the maintenance setting, so specifically oral proteasome inhibitors.

Esther Schorr:
Oh, boy.  Okay.  So now I’m going to drill down a little bit from a lay person’s standpoint about what you just said.

Dr. Krishnan:
Okay.

Esther Schorr:
It’s a lot of alphabet soup.  So I know that you’ve been doing some work with the drug daratumumab (Darzalex).  It’s a mouthful, and I know that that’s a monoclonal antibody.  And can you talk a little bit about what the relevance is about that?  Because I think our audience has probably heard of it but doesn’t know what’s happening in that area.

Dr. Krishnan:
Sure, happy to.  So daratumumab targets CD38, which is a protein on the myeloma cell.  So it’s very specific in terms of attacking the myeloma cell.  Now, that protein is expressed in other things like red blood cells, but really it’s very highly expressed on plasma cells, sort of the myeloma cell per se.  So daratumumab was already approved for relapsed myeloma, both multiply relapsed as well as patients who have a first relapse in myeloma in combination with some of the other drugs we think about such as bortezomib (Velcade) or lenalidomide (Revlimid).

This meeting this year, though, the big excitement is in regards to using daratumumab in newly diagnosed myeloma.  So we already know it’s a very effective drug in the relapsed setting.  We’re familiar with the toxicity profile, and overall it’s quite well tolerated, and so now the question becomes if it’s such a good drug should we move it earlier in the course of therapy to get the maximum benefit.

Esther Schorr:
So it could be a first-line therapy.

Dr. Krishnan:
Exactly.  So it’s already approved in the first-line setting in combination with Velcade, melphalan (Alkeran) and prednisone (Deltasone), so VMP, but that’s not a regimen we use in the United States.  So there’s going to be an abstract presented Tuesday, so I can’t even tell you yet because it’s a late breaker, but we only know a little hint of it which is using daratumumab plus lenalidomide and dexamethasone (Decadron) in newly diagnosed patients.  It’s called the MAIA study, and that’s the one that we’re all waiting to hear to see is that going to establish a new standard of care in the newly diagnosed front-line setting.

Esther Schorr:
So that helps me to understand that, thank you.  So then are there other studies that you’re involved in that would be interesting for patients to know about?

Dr. Krishnan:
So there’s another study that actually was presented yesterday.  It’s called the GRIFFIN study.  That uses daratumumab in combination with sort of I would say a quote/unquote standard regimen in the United States, RVD or lenalidomide, Velcade and dexamethasone.  And what it asks again the same question.  If you add to our standard backbone another potent agent, does it even further improve the responses?  So what they presented on Saturday was very early data on 16 patients, so we need to wait more, but it just shows you the excitement around that.  And that data they presented really was around the safety and suggesting that it’s a well-tolerated combination with a very high response rate, 100 percent response rate.

Esther Schorr:
Well, that would be my question then just as a care partner myself is when you’re talking about doing those kinds of combinations of two, three, four drugs are you all looking at the combined toxicity of those things and the side effects?

Dr. Krishnan:
Oh, yes, absolutely.  So the MAIA study, for example, very specifically looked at the three drugs of daratumumab plus len-dex comparing it to the two drugs, lenalidomide and dexamethasone, so–and the same thing with the GRIFFIN study.  That also was randomized so half the people got daratumumab in combination, the other half just got the standard RVD.

And there was, to be fair, a lightly higher increase in side effects when you added the daratumumab, a bit more infections and a bit more blood toxicity, so lower white counts.  So it is something to sort of, you know, take as a note of caution too, when you add more drugs that you do certainly expect that you are going to get more toxicity.  And obviously it becomes does the benefit outweigh the potential risk.

Esther Schorr:
As usual.  So I guess the other question I have is where does stem cell transplantation fit in all of this, or does it?

Dr. Krishnan:
So obviously I have a somewhat biased opinion.  I come from City of Hope, which is the largest transplant center in California, and two things I could say in terms of myeloma.  So we do over 8,000 transplants a year in the United States for myeloma, so it suggests that it’s a standards of care backbone of therapy.

As a transplanter I would say transplant still has the longest track record in terms of remission length and even if you compare it to standard RVD chemotherapy you get a longer remission when you throw transplant into that mix.  And I think what will be of interest to us is further improving upon that by either different maintenance strategies or induction strategies, so new treatment before the transplant as well to further improve the outcomes of the transplant.

And then the other thing I should mention, this is not a study that is open yet but it’s a study that we actually had some meetings about through the BMTCTCN, so a cooperative group of transplant networks, trying to ask the question.  So this is a group—you know, I used to chair the myeloma committee, and I’m still on the committee—we try and look ahead.  Right?  So we say, what can we do as a strength of network of transplant centers that patients really need?  What is the question they want to ask?  And one of the unmet needs is high risk-myeloma.  So whatever we do right now, and there’s been data presented at this meeting too, we need to do better.

For those patients who have advanced stage of myeloma, high-risk cytogenetic abnormalities, the therapy we have right now is still not optimal.  And one of the things that we’re going to do that we’re very excited about is we’re going to open a study that we’re literally going to go home and start writing in January, using CAR-T cells after an autologous transplant for patients with high-risk myeloma.

Esther Schorr:
So that gives—that’s hope for patients that have not had any real viable treatments till now or durable ones.

Dr. Krishnan:
I think that durable is what we would say.  So we’re all very excited about that.  It’s going to harness our strengths as transplanters, our strengths in cellular therapy and CAR-T and moving it up front.

Esther Schorr:
Good.  Well, thank you, Dr. Krishnan for all the work that you and your associates are doing.  I know that it’s, especially for myeloma patients and their families, it’s so important.  So thank you.

This is Esther Schorr from San Diego at the ASH conference.  Remember, knowledge can be the best medicine of all.

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.

Emerging Research and Promising AML Treatment Approaches

Downloadable Program Guide

Leading experts shared recent breakthroughs in AML treatment and research announced at the 2018 American Society of Hematology (ASH) annual meeting. The panel discusses new drug approvals, emerging clinical trial data, innovative, individualized approaches to treat distinct AML subtypes, and how these advances translate to the real world and impact AML patients.


Transcript:

Beth:

Hello, and welcome to today’s webinar. I’m Beth Probert. I am an MPN patient, was diagnosed a few years ago with polycythemia vera. Today’s webinar is where are we headed with the treatment of acute myeloid leukemia. What can patients look forward to for the coming year?

This is a Patient Empowerment Network program. And I’d like to thank our sponsors. As always, our sponsors have no editorial control over the content. Today, we’re going to talk about topics like recent breakthroughs in AML treatment and research announced at the 2018 American Society of Hematology ASH Annual Meeting. We’ll look at emerging clinical trials and how to access them, individualized approaches to treat distinct AML subtypes, and how will these advances translate for patients. You’ll also hear from AML patient Steve, as he shares his first-hand experience facing AML and how he’s doing now.

We will also answer viewer questions. And if you have a question, please keep in mind, we can’t get real specific with these questions, so try to keep them general, really geared more towards information and questions.

And we’d like you to send your questions throughout the program. We will try to answer all questions that come through. And if we can’t get to all of them, we will certainly address them through future webinars. Now, I’d love to introduce you to today’s guest. Our first guest is Dr. Naval Daver, associate professor, Department of Leukemia at the University of Texas MD Anderson Cancer Center. Welcome, Dr. Daver. I’m so glad you could join us today.

Naval Daver:

Hello. Thank you for having me. Glad to join.

Beth:

And our next guess is Leah Szumita. And Leah provides clinical trial support at the Leukemia and Lymphoma Society. So, Leah, thank you. I’m glad you can be here today.

Leah:

Thank you. I’m so happy to be here.

Beth:

And our next guess is our patient panelist, Steve Buechler, and he is an AML patient who has had a remarkable journey. Steve, welcome from Minnesota.

Steve:

Thank you. I’m happy to be here.

Beth:

Great. Well, Steve, we’d like to get started with you. I’d like for you to tell our viewers a little bit about your life with AML. And if you can include how did you get diagnosed, what was that like getting diagnosed, and how did you react, who is your support team, and just what you’ve been though. So, I’ll turn it over to you now.

Steve:

Well, at age 64, I was living what I thought was a normal, healthy life. I had no symptoms. My primary care physician had been monitoring my white blood cell count for a couple of years because it was borderline low but not too alarming. And then, in the spring of 2016, it began to drop more precipitously.

So, he recommended I see a hematologist, and I went to do that. And the hematologist said I should probably have a bone marrow biopsy. And so, I agreed to do that sort of to humor them because I didn’t feel sick. I didn’t have any symptoms. I didn’t have any idea anything was wrong. It was a memorable week. The biopsy was on a Monday. On Tuesday, I swam my normal 50 laps. I did some shopping. I ate dinner out. Wednesday morning, I played in a weekly poker game with some retired guys. So, life was normal, until that phone call that came Wednesday afternoon informing me I had acute myeloid leukemia, and I had to get to a hospital right away.

So, the next day, I checked into a hospital. The day after that, Friday, I started chemotherapy. So, in 48 hours, I went from feeling perfectly healthy to 24/7 chemotherapy drip. And they started me on this standard treatment that’s been use, I think, for a very long time called 7 + 3 Cytarabine and Daunorubicin to try to get the cancer into remission. And so, I spent a week on that medication.

And then, I waited for the inevitable drop in my white blood cell count and my immune system. I was going to be very vulnerable to various kinds of infections. And as predicted, I came down with colitis and an E coli infection, body rash, and a bunch of other stuff that they couldn’t even identify. But the infectious disease doctors stepped in and dealt with those issues one at a time. So, I ended up spending 5.5 weeks in the hospital for my counts to recover. But the good news was, one month after starting chemo, they did a bone marrow biopsy that found there was no residual leukemia. So, the first goal had been reached, at that point. I was in remission.

Adding to the story, of course, the first night I spent in the hospital, my wife was with me and left late in the evening to go home. And as she arrived home, she had a stabbing pain in her right leg. The next morning, she got up and could hardly get out of bed, called 9-1-1. They brought her to my hospital in an ambulance through the ER.

And it turned out she had a fractured femur. So, I was on one floor of the hospital in the chemo ward, and she was on another floor of the hospital awaiting subsequent surgery to repair her leg. And then, she went off to a transitional care unit for rehab. So, when I realized our house was going to be unoccupied for about a month, I started to write to our neighbors on email. And I found it was a really useful way to communicate. So, I ended up, over the many months that followed, adding maybe 60 people to that email list and sending over 60 emails out, over the course of a year and a half to keep people informed of what was going on.

I, subsequently realized, as I was writing for other people that I was really using that writing to make sense of my own experience. I struggled to figure out what was going on and how I could capture it and how I could explain to people. And it was useful to get their responses back, but it was useful for me. It was very therapeutic for me just to have that writing experience to make sense out of what was going on.

After 5.5 weeks, I got permission to leave. I went home for a while. But I was awaiting the genetic testing of my cancer to figure out what the next round of treatment would be. Because I think people know, with AML, there needs to be a second arm of the treatment. It can come back very fast and very ferociously. I was told that the genetic testing of my cancer would put me in either a low risk or a high-risk category for recurrence. And that would point towards either chemotherapy, if it was low risk, and stem cell transplant, if it was high risk.

When the results finally came in, they said, “Well, you’re kind of in an intermediate category.” So, the way forward was not as clear as I thought it might be. So, I talked to my initial oncologist. I did my own research. I, subsequently, went and talked to a transplant oncologist at the University of Minnesota Medical Center who sort of nudged me towards the transplant option. I went to the Mayo Clinic and got a second opinion. And all of the indications really were that I would be a good candidate for transplant. I had no comorbidity. I had no other health problems.

And everybody thought I should probably be able to withstand the conditioning fairly well. So, eventually, I came around to that decision to have a stem cell transplant. I had a brother who was a half match donor. But the folks at the BMT unit said we also have some good umbilical cord blood matches for you. And so, I was, again, faced with the decision about which way to go. But it turned out they had a study. Don’t they always have a study? I was randomly assigned to the cord blood donor option. So, my brother was off the hook.

And I ended up having a double cord blood stem cell transplant in October of 2016, about four or five months after I was initially diagnosed. That procedure went very smoothly. And within three weeks, a biopsy revealed that one of my cord donors was 99% engrafted, which is pretty early for a cord blood procedure. So, that was good news. I was able to go home, at that point, and begin a pretty long, extensive, and sometimes arduous process of recovery.

The first 100 days, they offered me to come back to clinic daily for the first month or so to get blood tests, to get platelets, to get red blood cell transfusions, whatever it is that you need to keep you healthy. It’s a pretty vulnerable time. One of the oncologists, at the transplant unit, described this whole procedure as, first, we bring you to the brink of death by killing off diseased immune system. And then, we try to bring you back again. Well, it worked, in my case, I’m happy to report. So, by early 2017, I was beginning to taper off my anti-rejection medication. That ended in April of that year.

And then, it was just a process of gradually getting more strength, getting better. And, in my case, very fortunately, I avoided any trace of graft versus host disease. So, that allowed me to have a pretty healthy recovery. One year after my transplant, of course, I had to go in and get my baby shots, my vaccinations and needles because my previous immune system had been obliterated. And they only gave me the dead vaccines, at that point, because they reasoned I couldn’t handle the live ones.

So, that happened at Year 2. And that was recently completed about two months ago. I got the rest of my vaccines. The other good part of the story is, although there was a 60 to 70% chance of graft versus host disease, I never had any trace of that. I’ve since become very active in talking with other patients as a volunteer, doing some writing, becoming involved in the cancer community. And I’ve come to appreciate really how fortunate my story was. I think the three big indicators were I got into remission on the first try. I’ve talked to a lot of patients who haven’t been able to do that.

My transplant engrafted within three weeks, which was a very solid, early result. And a lot of patients don’t have that kind of success. And I had no graft versus host disease. So, that’s about as good of a story as you can have with AML, as I understand it. So, obviously, I’m very grateful to have done that. And something like that gives me a lot of motivation to try and give something back. So, I’ve been participating in various ways in the cancer community.

Believe it or not, that’s the short version.

Beth:

Steve, you have a remarkable story. I just heard – we talked earlier, and just to keep hearing your story again is really just so noteworthy. And the three points you made, just having the early remission the first time with chemo is amazing. And early engraftment just within three weeks and no graft versus host disease. And your enthusiasm and wanting to give back and just with your writing. And we’ll talk a little bit later. I know that you have a book that’s coming out. So, your story is, for someone like me, amazing. But Dr. Daver, I’d like to turn to you, for a few moments, and tell me, is Steve’s story typical?

And what kind of feedback do you have on his journey?

Naval Daver:

So, Steve’s story is a very good outcome story. It’s not necessarily typical, as Steve mentioned. About 70 to 80% of our patients will go into remission with the first induction. So, it’s a high number, but it’s not 100%. And if you don’t go into remission with the first induction that is actually one of the very high risk or adverse features. It’s called primary refractory AML. And those patients usually do have a much harder time. The second thing is about 60% of patients will fall in what we call intermediate groups. So, we do do molecular and cytogenetics. And if we find that we have favorable molecular cytogenetic changes, then, those are considered to be good.

And we may not do transplant. On the other hand, if you have unfavorable cytogenetic molecular, then, it’s very clear a transplant probably is the only hope for long term survival. But, unfortunately, a lot of patients fall into intermediate group.

Now, that intermediate group is becoming smaller and smaller because we are understanding more and more about the molecular machinery, the cytogenetics, and the prognostic impact of new molecular mutations. So, we are able to triage patients better into high risk or low risk, which helps us make the transplant decision. But I think the most fortunate thing, in Steve’s case, was the lack of GVHD. And that actually is very uncommon. Most of the patients we see will have some degree of GVHD. It may be acute. It maybe chronic. In most cases, I will say that it is manageable. We rarely see very severe ICU requiring GVHD or fatalities from GVHD.

But about 60 to 70% will have some degree of GVHD, will require some treatment for it with steroids or additional immunosuppression. And in some cases, it can take many months and can be a major discomfort and affect quality of life. So, I think that was fantastic that he did not have the GVHD. And I think all of those features, although are seen in a traditional AML story, I think Steve was fortunate, and the outcome was very favorable so far.

Beth:

Great. I really like that feedback. And what I wanted to ask you, as well, in regard to the no graft versus host disease, you said about 60 to 70% will actually encounter that. So, am I correct in assuming then that, when you do a transplant with someone, you account that that’s probably going to happen, the graft versus host disease and you have treatments and things lined up in anticipation of that happening?

Dr. Daver:

Yeah, absolutely. When we do the stem cell transplant itself, we actually do prophylaxis for graft versus host disease. Almost all patients will be on steroids, some form of immune prophylaxis. It may be tacrolimus. It may be sirolimus. There are some newer drugs. And in spite of that, if we see graft versus host disease, we have some very good medications.

In fact, some recent drugs approved such as Ruxolitinib, Ibrutinib, etc., which can work. But in spite of all of that, I would say a majority of patients do face a struggle with graft versus host disease. And they do have some degree. Now, again, it may not be severe. It may be in the form of graft versus host disease of the mouth, which causes your ability to eat to be decreased, or it may be the skin, which may be itchy or uncomfortable, or it could be ocular, which causes eye irritation and burning and requires eye drops. So, they may not be severe, but they hugely do cause discomfort of that quality of life.

But yes, we do try our best to avoid it. And in some patients, we are able to get away with none. And in some patients, they will have mild to moderate, which has to be treated. Luckily, with the newer generation of immune prophylaxis monitoring treatment, we have very few severe graft versus host disease, which is a good thing.

Beth:

Great. I’m so glad you touched on that. So, I wanted to shift gears a little bit, Dr. Daver, and find out from you what are some of the key takeaways for AML patients and care partners from ASH.

And I also wanted to say what I’ve heard a lot, in regard to AML is that, for almost 40 years, there was just a standard way of treating. And all of a sudden, in the very recent years or maybe year, I’m hearing that there’s so much now, new drugs and things happening. So, would you mind touching upon some of those key takeaways?

Dr. Daver:

Absolutely. I think, this year 2018 was clearly the year of AML. There’s just, compared to all of the other malignancies, in the last two years, there’s just been a huge amount of progress in the way of approvals. Now, what I do have to say is, although we are seeing the fruits of a lot of efforts, actually, the research in AML has been very intensive for the last 15 to 20 years. And what we’re now seeing is really the combination of a lot of those efforts. Molecular, immune analysis, which have led to these drug approvals.

But today, really, I think, compared to even three years ago, when we did not have a number of these drugs, the whole outlook for treatment of AML has changed dramatically. So, we’ve had eight new drugs approved in a few years. And, to put it in perspective, for the 40 years before that, we actually really had almost no drug approved. There was one drug, Gemtuzumab, approved, but it was actually withdrawn from the market. So, when they say when it rains, it pours, that kind of really did happen, in the case of acute myeloid leukemia. But what’s really important, I think, I that there are now a number of targeted therapies towards particular mutations.

And some of these have actually been approved, in the frontline setting. So, now, it has become very important that we don’t just treat all AMLs as one disease. In fact, that’s something we knew for about 20 years that AML is one of the most heterogenous of all malignancies. Lung cancer and AML, these are probably the two most heterogenous cancers where it’s not really this is AML, it’s different types of AML, which can have prognosis of 95% cure rate all the way down to 10 to 15%.

So, identifying these groups was very important for prognosis. And that’s something we have been doing but more important for treatment. So, for example, a mutation that is called an FLT3 mutation is very, very important because, on its own, it is associated with an adverse prognosis. These patients had high white counts, proliferative disease, and their three year or five-year survival was usually 20 to 25%, when we first identified this mutation in 2001. Now, there are new drugs called FLT3 inhibitors that specifically inhibit the FLT3 mutation pathway.

And with the addition of FLT3 inhibitors, specifically a drug called Midostaurin that was FDA approved 1.5 years ago, plus stem cell transplant, and even more so, at the recent ASH 2018 meeting doing post stem cell transplant, FLT3 inhibitor, when we do all of these three interventions, we’re now getting up to five year plus survival rates of 75%. So, this is amazing.

The patient who was 25% 12 years or 13 years ago, when we first identified this mutation, could today, if appropriately treated with FLT3 inhibitor transplant and FLT3 inhibitor maintenance, could be in a 75% long term survivor rate. So, tripling those outcomes. And similar things are being seen for other groups. For example, APL, acute promyelocytic leukemia, is one disease where we actually are able to treat these patients without chemotherapy. So, you can give a combination of ATRA arsenic, which gives you 95% cure rates.

So, the key now, and what I tell a lot of our community doctors, our fellows, other academicians is it’s not about just rushing in treatment, which has been the paradigm for 30 or 40 years, but more important, it identifies specific molecular mutations or cytogenetic changes and choose the best treatment because the impact of choosing the appropriate molecular or non-chemotherapy or antibody based treatment is, actually, much more than quick therapy. And I think that message now is going out.

And things are improving overall.

Beth:

Wow. And what I’m hearing are two things. Eight new drugs, however, those eight drugs are specifically going to be used, in regards to different mutations. And so, my question to you is it’s very obvious that genetic testing, for these mutations, is a huge puzzle piece to this. And could you talk a little bit about that. At what point can a patient get this genetic testing from the mutations. And if you could just speak to that because it just sounds that is essential?

Dr. Daver:

Yeah, absolutely. I think that is probably the No. 1 takeaway for both patients, caregivers, and physicians. So, the genetic testing should be done for all new AMLs at the time of diagnosis. And there are a number of different labs across the country, commercial labs, that are able to do this new genomics, foundations, hematologic, all of these are not insurance approved and covered.

Some of the larger academic centers have their own molecular testing analysis. The most important thing is that we should usually wait for these results before rushing into therapy. And just to give an example, when we see a new AML at MD Anderson, we will rush their cytogenetics and molecular testing. We’re looking for cytogenetics to rule in or rule out APL, acute promyelocytic leukemia because this can be treated without chemotherapy with 95% cure rates. The other big group we’re looking at is what we call core binding factor leukemia. These are a group of specific chromosomes associated leukemias.

And if you find those, then, that is the group or the addition of the antibody treatment called Gemtuzumab Ozogamicin or Mylotarg, which is FDA approved, can improve the survival rates by almost 20%, which is a huge amount on top of chemo. So, you don’t want to miss identifying this core binding factor of chromosomes. Then, if we don’t find one of these two, then, we rush our molecular panel.

We are fortunate. We get the molecular results in 48 hours. That’s one of the places in the country. There are a few other groups that are in the same range. But even in the commercial setting, I know for a fact that they’re able to get these results in six to seven days. So, I think it is actually possible and feasible. And even on some of the large trials we’ve done across 100 plus centers, we were able to safely wait for those results. Two molecular results were most important looking for our FLT3, if you find that mutation. We want to add the FLT3 inhibitor up front, and then, IDH1, IDH2 mutation.

And if you find those, we may consider, on a trial basis, adding IDH1, IDH2 mutations. And then, if none of those mutations or chromosome groups are identified, then, we will consider standard treatment. But even there, we have trials where we’re adding new drugs, which have shown very high activity like Venetoclax or Nivolumab or immune therapies to standard chemo. So, really, this is now personalized therapy. There are five clear subsets of AML that will have different treatment approaches.

And addition of the appropriate agent could improve your survival and cure rates from anywhere from 10 to 30 or 40%. So, I think this is quite important.

Beth:

It’s just amazing. And what I’m also picking up on, and what I’ve been told about AML, is that you need to move quick. This is, once diagnosed, time is of the essence, and especially with the different subtypes. So, we’re talking about genetic testing. And I really, really was very interested in hearing how it works and how quick it could be turned around. But what would you say – we very often hear, like in Steve’s case, it was his doctor who referred him to a local hematologist and then, eventually, to a specialist? Sometimes, we hear people being rushed to the hospital or going to their local doctor. But time is of the essence, in getting this genetic testing.

What advice do you give patients who, typically, might go to a local doctor, how to move along in this process and how to advocate for that genetic testing? Do you have any feedback on that?

Dr. Daver:

Yeah. I think there’s a fine balance. And that’s where it’s hard to make a generalized recommendation across the board because there are some AML patients who come to us who have a very high white count, more than 100,000, for example. They may have evidence of leukemia already infiltrating their liver or kidney, with organ abnormalities and lab changes. And in those patients, we may have to start treatment very early. But those are the minority. We’ve published, as other groups have looked at this, those make up about 5 to 10%. So, in the majority, it is, actually, a mindset change.

And this is something we’re doing a lot of education on, as well, is that that mindset of the sun should never set on AML. We have to treat right away, actually, was true, when you didn’t have other effective therapies that could be added that could change your outcome from 25% to 75%.

But today, in fact, I think it’s much more important to select the appropriate treatment or the addition of the appropriate molecular immune therapy than rushing into treatment. In fact, our group, as well as a number of other groups in the country, have published it. So, what we recommend, in general, is we get a new AML. We would admit those patients. I still think this is an inpatient disease. We would monitor them closely. We send, on the same day that we see them, a molecular chromosome panel. We ask it to be rushed. And then, usually, we can get these results in three to five days.

And I would wait to get those results because, based on those results, we may choose a FLT3 inhibitor. We may choose the antibody Gemtuzumab. We may choose IDH therapy. We may choose ATRA arsenic. So, I think, for most patients, what you could do, of course, you have to be careful when you’re discussing it with a physician, you don’t want to push on them too much. But I think it’s important to ask about molecular therapies, molecular trials, whether we could get the molecular information early, and how we could incorporate that.

I think, the good thing is we’re seeing, across the country, most of the physicians are taking this approach. And there is very intense education. But I still think it doesn’t hurt to ask about it and make sure that that testing is being done because I think it could make a huge difference in your outcome.

Beth:

Great. Wonderful feedback. Now, Leah Szumita, I’d like to bring you in on this conversation because we heard eight new medicines right now. That’s huge. And as Dr. Daver said, those are the results of clinical trials. And, recently, I heard that only about five to eight percent of adult cancer patients are participating nationwide, in the United States, in clinical trials. That seems like such a small number. And we depend on these patients to participate in these clinical trials to come out with these eight new meds.

There’s definitely a gap. And I’d like to hear your feedback about just that. And then, if you can go into – I’m going to ask you a few more questions about how people get involved in clinical trials. So, take us through that.

Leah:

Great, I will. So, I have to echo Dr. Daver’s sentiments about the importance of the genomic testing as well. And really, the new breakthrough in AML therapy is just a testament to the ongoing research. As he said, the research has been happening for 15 or 20 years. And we’re finally seeing the fruits of the labor. So, it’s encouraging. And that five to eight percent is low, but there’s room for improvement. And I think many different organizations have identified barriers to why these enrollment rates are so low. I will say that, of all of the clinical trials, somewhere between two and ten percent of clinical trials have to close because of low accrual rate.

So, there is just serious work to be done. I think, you can look at barriers in two different ways. There are patient barriers. There’s just a lack of awareness that clinical trials exist for all stages of diseases. So, many people believe that a clinical trial is only for those who have exhausted all other treatment options. And so, that’s actually not true. There are trials for every stage of disease. Previously untreated, newly diagnosed, relapse refractory, maintenance and remission. There are other barriers that people are afraid to be a guinea pig.

And so, I think, as healthcare providers, that’s our job to really educate that clinical trials are very controlled, closely monitored situations, provide education on the different phases and what those mean. There are very complex and stringent inclusion/exclusion criteria to clinical trials, which, in one way, can make it very difficult to understand, if you’re even eligible for a trial.

And so, that’s why clinical trial nurse navigators, such as myself, can really help patients and caregivers sort through that information. And then, sometimes, physicians aren’t aware of all of the trials that are out there either. And that is not to slight practitioners, but, again, it’s just an overwhelming amount of information. It takes time to stay on top of all of this research. It takes time to go through all of this research and all of the different protocols.

And so, it’s really important for patients and caregivers to have an advocate to try to identify what clinical trial is right for them.

Beth:

And so, through the Leukemia and Lymphoma Society, you offer this service, if I understand you correctly. So, patients and their caregivers can reach out to your department and find out what is there for me. What comes to mind, also, I hear quite often, and we’ll get Dr. Daver’s opinion on this as well, in just a moment, but there seems to be roadblocks to people, not only I don’t want to be a guinea pig and understanding that piece of it, but also are there some financial hurdles, geographic hurdles?

I hear from patients, quite often, that I live so remotely. I’m in a rural area. How would I manage this? So, could you give a little feedback about that?

Leah:

Sure. First, with regards to the financial barriers, another common myth is that a clinical trial is free. And, unfortunately, it’s not. I would say that, often times, whatever is being studied, either a new drug or a combination of drugs that usually is covered by the sponsor of the trial. But the rest of the care needs to be billed to insurance. And then, there’s this third bucket of cost, which is the money it takes to get someone and their family members to and from all of these appointments, prolonged hospital stays away from home. So, those are significant financial barriers to participate, in a clinical trial.

There are resources out there to help navigate through some of these obstacles. And, again, I would encourage people to contact Leukemia and Lymphoma Society. We can help steer you to those resources. With regards to the geographic barrier, it’s correct. A lot of these large, academic medical centers are not in proximity to people in rural areas. And that is one key point of clinical trials that needs to be improved upon. And I think a great goal would be to get some of these later stage, later phase trials out into the community setting where they may not require quite as intensive monitoring.

But it can also be available to more patients and really diversify the patient populations.

Beth:

Great. Really great feedback. And then, Dr. Daver, I know that your center is very proactive with communicating clinical trials to patients. And could you just speak about that a little bit?

I know it must be overwhelming. You’re doing your research. You’re a clinician working with your patients and to keep on top of every clinical trial. But, again, I know that that’s something you’re very, very on top of. But could you give a little feedback about how you approach that?

Dr. Daver:

Yeah. As an AML expert, I would still say I’m not really aware of every AML trial, in the country. It’s not possible. There’s 200 or 300. And they keep changing every week. So, nobody really, at a clinician level, is going to be completely aware. Now, what we do know is the comorbid areas, the targeted groups, the particular mutational groups of trial, the new trials, and, of course, what’s looking more exciting, whether it’s in Phase 1, Phase 2, or Phase 3 development. I completely echo the sentiments. I think 100% of our efforts should be to get patients on trial. And, at MD Anderson, we have 180 trials in leukemia alone of which about 70 or 80 are in AML.

And, of course, this is on the higher end of the spectrum. But the focus is really to enroll people on trial. And, I think, what patients often, and I hear this almost every day in clinic, is that they’re concerned because, when you say a trial, they are thinking experimentation. I think there’s a big difference in experimentation and clinical investigation. So, our effort is always to offer trials that give you standard of therapy plus something. And, in fact, whenever we’re treating a frontline patient, no leukemia expert, least of all, in a very large academic center, is going to randomize the patient to something other than standard of care.

But what we do want to see is can we improve the standard of care. And that’s how all of these new drugs go approved. So, we were doing these trials with FLT3 inhibitors added to chemotherapy for almost 10 or 11 years at some of the large centers in the country. Similarly, with IDH inhibitors or Gemtuzumab. And I have many patients who, seven, eight, nine years ago, were able to go on these trials, many, many years before the FLT3 inhibitors approved and get those benefits.

So, the way we like to put it is to try to get you tomorrow’s therapy today. So, you’re going to get access, approximately, four to five years before a drug is approved. And almost always, you will get the standard treatment plus something. So, you’re not going to get less. You’re going to get more. Now, of course, all of the additions may not work. But the chance is that at least you’ll get the benefit of standard agent plus something. And a lot of times, when we explain that, then, patients, of course, say I would like the trial rather than just standard of care.

The other thing is, with the cost, although it’s true that the drugs may not all be free, at least you may get some or part of, in some cases, all of the drugs free. So, at least there is some incentive there because, a lot of times, people say the insurance covers it. But the cost of a lot of drugs is astronomical. And even if you’re paying just 5% for an average AML drug targeted therapy, which is somewhere between $15,000.00 to $20,000.00, that 5% can be $1,000.00 to $1,500.00 a month.

So, a lot of times, what I see from my patients is, when they go on our trial for FLT3 inhibitors and IDH inhibitors, and even the fact that they’re not paying their co-pay, often offsets their cost of coming to MD Anderson or coming to Dana Farber or Sloan Kettering or whatever it may be. So, I really think that one should definitely talk to the Leukemia and Lymphoma Society, other major organizations, so that they can find out what trials are there. And many times, patients say, well, don’t think there’s a trial for me, or their local physician may not be aware.

And I can guarantee you, almost 99 to 100% of the time, there will be not just one but many, many trials that are available to you. So, I think that little bit of effort, emails, phone calls can go a long way.

Beth:

Great feedback. And Leah, going back to you, excuse me – I’m sorry. I just need to stand up a moment. I’m in a room that decided the lights would go off. But you can all hear me. Speaking to you, and I’m getting towards our lights, can you talk about what questions someone can ask their doctor, in regard to clinical trials?

What are those important questions?

Leah:

Absolutely. So, there are so many of them. And one of the things that my group of nurses and myself do is really provide people with education about the basics of clinical trials and then, the language and the questions they can use, when they go back to their provider. And then, also, when they go to make that connection with the clinical trial group. So, the list is long. I would say first and foremost, asking what the risks and benefits are. Many times, in a clinical trial, there are different requirements about how often someone might come to and from the site, what the finances might be related to that.

Also, a lot of studies or drugs used in studies have been used in other studies. So, asking if there are any early results or any results from prior studies using those medications is important.

And asking about how this may affect quality of life, all of those different kinds of questions. There’s a very long list. We do have a fabulous clinical trials booklet that patients and caregivers can obtain that have lists of questions. And we always encourage people to read through that material as well. But knowledge is power. So, the more knowledge and research someone does, and bringing someone with them to these appointments to really take notes because it can be so difficult to absorb all of this information, would be some of my recommendations.

Beth:

Wonderful. Great feedback. So, Steve, I’d like to circle back to you now. You have this overwhelming, very intense journey. Where did you get information about AML? Where did you get support? We hear that so often, when someone is diagnosed, and they have to handle and make decisions fast, what kind of resources did you utilize. And tell our viewers out there, so the can understand what to do and how to do it.

Steve:

Well, one thing I did not do is go on the internet and scare myself half to death. I trusted my doctors. It did happen so quickly that I was in treatment before I even understood the nature of my disease. So, for better or worse, I was getting on that train and going wherever it was going to take me. But I had a great team of social workers. I had great nurses. My oncologist was excellent in spending as much time with me as I wanted. And so, it was a gradual kind of learning curve for me. And the fact that the early treatment went pretty well, obviously, helped give me confidence.

And the same thing, when I went down to the University of Minnesota Medical Center. They gave me a very thorough explanation of what was going on, recommended the stem cell transplant. I had a colleague whose father actually worked in this area decades ago.

And I talked with him. He stressed the importance of getting a second opinion. So, I was able to go to the Mayo Clinic, which is about an hour and a half drive from where I live. And I talked, first, to a hematologist who said I can tell you some things, but you should come back and talk to the transplant experts here. So, I did that as well. So, between my initial oncologist, my transplant oncologist, my second opinions at the Mayo Clinic, I was pretty confident that not that it would all work out, but this was the best path to follow. And as I followed that path, I did get invited to a clinical trial.

Just from a patient’s perspective, some years ago, I was the caregiver for my mother, as she was struggling and eventually dying of breast cancer. And her oncologist wanted to put her in a clinical trial. And I was very suspicious, and wondering is she not going to get the kind of care that she needs because you want to use her as a subject in a study. And I declined that study. And some years later, I find myself being invited to join a study. And I asked a lot of questions, especially when I saw that 22-page consent form.

That’s pretty daunting. There’s a lot there, and there’s a lot to ask about, and I did. And people patiently answered my questions. And I just came to realize, essentially, in my case, the trial wasn’t even close to experimental. What they were saying is this is how we’re going to treat you regardless. But if you’re willing to do the study, we’re going to track the results. And that can help people down the line. So, at that point, it seemed almost like a no brainer. And I could have chosen my brother as a donor or a stem cell as a donor. Instead, I went into a study that randomized me. And I went into the stem cell, and it turned out just fine.

But they said the five-year survival rates for either path are about the same, so that’s why we’re doing the study to try to figure out what the different pathways are to that outcome and when something will benefit patients in the future. So, at that point, it just seemed like a reasonable thing to do. Helping people understand that you’re going to get the best treatment they can give you regardless, even though you’re in the study. I think that’s, for many patients, the key point. And it sounds like Leah and her folks are working on that angle.

That’s really important for patients.

Beth:

Wow, that is fabulous feedback. And if you could say – what I’m hearing you say is that you got a lot of support from, it sounds like, the hospital where you received your care. That there was you mentioned social worker, and they sounded like they were really there to give you support. Would you agree that everyone really worked together to help you through this journey?

Steve:

They did, both the professionals and circle of friends and colleagues. Of course, those email correspondences, as I said, I was getting multiple responses to every email that I sent out, from various people. Sometimes funny, sometimes dark humor, which I especially appreciate. Thank you, Dave, from Milwaukee. So, a variety of things that came in, people prayed for me. I’m not especially religious, but whatever they wanted to do was fine with me. So, the writing, again, was therapeutic.

I practiced a lot of mindfulness and meditation and yoga. I was a very active patient. I walked the halls five miles a day. When I couldn’t leave my room, I was on a treadmill. I just needed to do things that sort of kept my body up and moving. And I think that really helped my recovery. I had nurses tell me, at one point, I was doing better than any other patient, at that stage in treatment. I’m not bragging about it, but I think, again, initial good reactions made it easy to get in this upward spiral. I exercised, I ate as well as I could. And I’ve seen patients have a bad time. And they’re kind of in a downward spiral.

And it’s really hard to reverse that. If you don’t feel good enough to teat, if you don’t feel good enough to exercise, it’s really hard to get out of that box. And so, anything you can do or anything nurses or social workers can do to help patients be proactive, be as active as possible, ask lots of questions, in whatever fashion suits their needs. Try and tell your story, whether it’s Caring Bridge, or emails, or verbal recording of what’s going on, I think there’s a great therapy to just trying to put together, from a patient’s perspective, what the hell is going on here and what’s happening to me and how might it turn out.

And those are some of the things that helped me get through.

Beth:

That is just great feedback. And Dr. Daver, I’m picking up that Steve has just an amazing attitude. And what kind of feedback do you give about that? These patients, these wonderful people, their lives have been turned upside down. As you tell us, it’s just very quickly, they’re living one life and now another. How much do you see, listening to Steve’s attitude and trying to be proactive and advocate for himself, do you feel that’s an impact on overall success in treatment and moving forward?

Dr. Daver:

Yes, absolutely. I think that the attitude plays a major role. But I think a few things that Steve said are very important.

One is that he did seek out second opinions. He did go to Mayo Clinic, a very large academic center. He got additional input. He learned about clinical trials and outcomes. And a lot of times, we have patients who may contact us or physicians from outside who contact us or come to us. And sometimes, we may not have something different to offer. There may be a standard treatment. A lot of times, the peace of mind of knowing that you have consulted with a large academic center, one of the top centers, whether it’s Mayo or MD Anderson or Sloan Kettering, whichever it may be, often helps a lot.

And then, there may be other times when we actually do say, and this happens quite frequently, that, actually, we have a trial that I think will be a better FLT3 inhibitor or better IDH inhibitor or a better antibody. And this is what I would do, if I was in your place, or if I had a relative in your place. So, I think that helps your peace of mind and your mental framework. And the second thing is – and that’s not something we can control is how you do to the initial treatment.

If you have good responses, if you tolerate it well, then, of course, we do see that those patients are always more optimistic, have a better mental framework, it helps. But I also see that there are some patients who come in, with a very negative framework. And that’s where I think learning that there is so much new progress, that there are so many options, not only in the frontline setting, in the relapse setting, in the maintenance setting, even after post-transplant relapse. We have things that, potentially, could cure patients, which we didn’t have even five years ago.

So, I think knowing that there’s a huge amount of progress, that the cure rates have doubled, tripled, in some cases, in elderly AML and FLT3 AML. And no longer having AML is the end of the world. In fact, in our most recent data update that we are going to publish soon, we see that, in the young patient, 65 and below, the overall survival, if you gave all patients who visited MD Anderson is about 66%. So, 23 patients actually had a long-term cure.

And people are shocked, even physicians I know of in the ICU and ER settings, don’t realize this fact. In elderly AML, it’s tougher, but we are going from 10% to almost 45 or 50% cure rates in patients 65 plus. So, I think, once people hear these numbers, they completely change their mind and are much more optimistic. But getting that information across to patients, to caregivers, to make them do the referral or make them consider treatment, I think, is the first big hurdle that we have to kind of overcome.

Beth:

Wow. And that is just very right on target. So, I’d like to shift gears a little bit. We do have a few questions we have time for. And Dr. Daver, the first question I’d like to get your feedback on, and forgive me with the pronunciation of the actual medication, I’ll try my best. So, this question comes in, what is the role of Venetoclax, if any, in treating AML. And when might that be FDA approved, from what you might know about this?

Dr. Daver:

So, the Venetoclax is probably one of the most exciting drugs in AML, especially elderly AML. In elderly AML, it is the most exciting drug that we have had probably forever. So, we used to treat elderly AML, meaning above 65 years of age. And these are hugely people not just by age, but also based on the physician’s review who are considered not fit for intensive chemo. They may have kidney problems, liver disease, poor performance status, immobility. And so, we cannot give the high chemo, the 3 + 7 that Steve got. And we have to use lower intensity therapy.

And we used to use Azacytidine alone, with the response rate of about 20 to 25%- and 3-year survival of about 15 to 20%. And now, we’ve done a study using Azacytidine in combination with Venetoclax where the response rates were 73%. So, going from 25% to 73% not doubling or really tripling, and that the survival is now 46 or 48% going from 15 to 18%.

So, that’s a huge, dramatic shift, three times response rate, three times of the potential cure rates. So, I think, right now, we believe that Azacytidine and Venetoclax really should be the standard of care for elderly AML, if they’re not going to get induction chemo. And, in fact, it was FDA approved very recently. So, three weeks ago, in fact, right before the ASH meeting, end of November, Azacytidine in combination with Venetoclax, as well as low dose Cytarabine and combination with Venetoclax were FDA approved.

And I think, now, with the approval, although we were doing this even before the approval, no elderly AML patient should get Azacytidine or low dose Cytarabine alone. I really think addition of Venetoclax now is the standard of care, triple response rate, triple survival. There’s no reason not to do that.

Beth:

Wow. That is an amazing shift and such good news for our elderly patients. That is great. I do have another question. And I believe it’s targeted for you as well, Dr. Daver.

For those young folks, under 35, who relapse quickly, within about 100 days after MUD allo transplant for AML, M5, no mutation target, what will be a sustainable way to buy time and bridge for that next transplant. Could you talk a little bit about that?

Dr. Daver:

So, that’s a very tough scenario. Relapsing post-transplant itself is a very high-risk feature. It, basically, indicates that disease is aggressive and may not respond to further chemotherapy or transplant. But relapsing early post-transplant, which we usually consider within 100 or 120 days is actually quite an adverse feature. So, for those patients, I think the best chance is if we can find a targetable mutation. So, we will be looking for FLT3 or IDH1, IDH2 mutations. If we find those, then, I think we do have some chance with either a FLT3 inhibitor alone or, more likely, in a FLT3 inhibitor, in combination with low intensity therapy.

And there are a number of these agents either approved, but I would actually go for a trial where we’re combining either FLT3 inhibitors or IDH1, IDH2 inhibitors with other exciting agents like Azacytidine and Venetoclax. I think that will be the best shot of getting a long-term remission, potentially, a second transplant. Of course, there are a lot of caveats and variables. And you have to look at the individual patient to make that determination. The other group of therapies that you could use, if we don’t find the FLT3 or IDH because only about 30 to 40% of patients will have one of these three mutations, is immunotherapies.

And these can work really well, especially in the post-transplant relapse setting. And we have drugs such as antibody drug conjugates. These are antibodies that carry a toxin and can attack the leukemia cells. Or what we call immune check point antibodies. They’re also agents that activate your own immune system post-transplant to fight against tumor. And with these, we have seen some very exciting activity, specifically, in the post-transplant relapse.

And a lot of these are all under clinical trial setting because the antibodies and the immune checkpoints are not yet approved. They may be in the next couple of years. So, I think this would be an ideal scenario to find the academic center close to you and try to consider getting into one of the trials, either targeted therapy or immune therapy.

Beth:

And another question would be do you see post-transplant relapse more in specific mutations? Are those with specific subtypes of AML?

Dr. Daver:

Yes, we do. So, we see the post-transplant relapse most common in what we consider the adverse risk AML. So, the adverse risk AML are the patients we definitely take to transplant. But, unfortunately, even after transplant, they remain the group that have a high risk of relapse. So, these are patients who have what we call TP53, one of the worse mutations. They will often have a high risk of relapse post-transplant or chromosome changes like deletion 7, deletion 5, deletion 17, also another high-risk group.

And the third group is what we call secondary AML. So, there are two ways you could get AML. You could have spontaneous AML, most common. We have a patient, no prior history of chemo radiation, other cancers, who comes in with acute diagnosis of AML. But then, there’s another group making about 20 to 30% called secondary AML. So, these are people who have prior breast cancer, colon cancer, bladder cancer, and got either chemotherapy or radiation for that. Or people who had prior MDS, which is an AML precursor and then, developed AML.

And these people who have secondary AML are much more risky and also more prone to relapse post-transplant. There are a few new drugs like Vyxeos that can work well, in this situation. But, in general, these are probably the high risk molecular or morphological groups that could relapse post-transplant.

Beth:

Very interesting. Well, I so appreciate all of the wonderful information and feedback that our guests have provided today.

And the timing is great. Just coming off of ASH has been extremely encouraging, Dr. Daver, with you sharing all of these wonderful new eight new drugs and insight that’s going on. And, Leah, your feedback has just been phenomenal. And really, I believe it’s going to ease people’s concerns and fears about clinical trials, and between you and Dr. Daver speaking about the clinical trials, why they’re so essential, and they’re doable. And, Steve, your feedback, not only about clinical trials, but your journey is phenomenal. And I hope our viewers look forward to seeing information.

We may not have mentioned this. Steve has written a book soon to be published about his journey. He has some very interesting feedback that we just didn’t have enough time to share on today’s webinar.

So, thank you, again, to our guests and our sponsors. And a replay will be completed soon. And you’ll receive it via your email. So, our audience, please look forward to that. And remember, be your own advocate. Thank you.


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

ASH 2018 – Tools for Staying Up-to-Date on CLL Research

CLL patient advocate, Lee Swanson, interviews Dr. Anthony Mato, Director of the CLL Program at Memorial Sloan Kettering Cancer Center about the exciting news for CLL patients at the ASH 2018 meeting.


Transcript: 

Lee Swanson:

Hello.  I’m Lee Swanson at the American Society of Hematology conference in San Diego joined right now by Dr. Anthony Mato from Memorial Sloan‑Kettering in New York.  And, Doctor, CLL, what’s come out now at this conference about CLL that patients want to know about?

Dr. Mato:

This has been a very exciting ASH meeting for patients with CLL.  There’s been a couple of big themes, but probably the largest is the comparisons of novel agents to chemoimmunotherapy combinations.  We saw two presentations looking at ibrutinib and rituximab as compared to the chemo combo FCR, which is a standard of care for patients who are young and fit, and we also saw a comparison of ibrutinib with or without rituximab, the antibody, compared to bendamustine Rituxan.

The overlying theme of the two presentations is that the patients who received ibrutinib tended to do better, certainly in terms of progression‑free survival and even in terms of overall survival with regards to the FCR comparison.  So a big theme is that there are fewer and fewer patients who are the right candidates for chemoimmunotherapy, and it appears that BTK inhibitors, at least as of this moment, will be the standard of care frontline for patients with CLL.

Dr. Mato:

So the good news and the bad news:  You don’t have to do chemotherapy.  On the other hand, chemotherapy is a defined six‑, seven‑month regimen.  Does this mean you’re taking a pill forever?

Dr. Mato:

Based on the current way that ibrutinib has been studied and labeled that means you’re on a long‑term‑‑it’s a long‑term commitment to ibrutinib.  There have been updates at the meeting of ibrutinib‑based and venetoclax‑based combination therapies where there is the hope that giving ibrutinib with a partner, for example, or venetoclax with a partner will allow us to treat to a fixed duration and then stop for patients, and that duration would either be based on some predetermined time point or on depth of response based on response criteria or minimal residual disease criteria.

So right now it’s a long‑term commitment, especially frontline.  In the long‑term I think we’re headed toward the direction where we can define which patients may stop sooner and then be retreated.

Lee Swanson:

If you stop, can you be retreated with the same?

Dr. Mato:

That’s a great question.  There’s not a lot of information about that, but there’s no reason biologically to think that that wouldn’t be a problem.  Specifically, if you stop in the setting of responding disease it’s not likely you’ve required resistance to that drug, and so retreatment should be a reasonable strategy.  We’re at Memorial Sloan Kettering now designing many trials that will try to answer those questions and allow us to stop either monotherapies by themselves or combinations to treat to a depth of response and then stop, so that’s something we’re really interested in.

Lee Swanson:

So if a patient gets a diagnosis now from‑‑sometimes from a primary care physician, of CLL what’s the conversation they should have?

Dr. Mato:

From the primary care physician?  Well, I think the primaries are great at identifying an elevated white blood cell count and the signs and symptoms of CLL even making the diagnosis.  Flow cytometry is readily available now to anyone who wants to order it.  I think the conversation with a primary care physician should be who should that patient see as a CLL expert to help guide the observation period which is important, as many patients are not treated initially, and also to help them to be informed as to how the field is changing.  Because the progress is so rapid you really need to have someone who is focused in on this area to help guide that particular management strategy long term.

Lee Swanson:

It’s important to get to a specialist, at least get a communication with a specialist.

Dr. Mato:

Exactly.  And of course the local oncologist and the internist are very important in terms of patient management, but ultimately there could be somebody who could help drive that‑‑some of the more important decisions based on the newest standards.

Lee Swanson:

So all of these things coming out, how does a patient keep up on what’s going on?

Dr. Mato:

That’s a really great and difficult question to answer because there’s so many different sources of information, some more reputable than others on advances in the field.  I think that probably the best source is having a physician, a trusted provider who is up to date, who can help interpret some of the more complicated findings from the research studies.  But in addition there are patient organizations and professional societies who are reputable, who provide up‑to‑date, very reasonable recommendations, either through their websites or through the literature that they provide for patients.

I think trying to avoid just general Google searches for advice on management of CLL is a good idea to not do.  I find that oftentimes things that get posted online can be just one‑off examples where somebody’s either extremely happy with care or very unhappy with an event, and it may not necessarily be representative for all patients.  So I would say professional societies, CLL focus, patient organizations, and then of course having a care team that’s very focused and very specialized in the area so that they can interpret what can be complicated.

Lee Swanson:

Okay.  Thank you very much, Doctor.  Appreciate your time.

Dr. Mato:

Thank you very much.  Yep.

Lee Swanson:

This is Lee Swanson.  I’m at the American Society of Hematology conference in San Diego.

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 – 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.