Tag Archive for: cytogenetics

Essential Imaging and Chromosome Tests after a Myeloma Diagnosis

Essential Imaging & Chromosome Tests After a Myeloma Diagnosis from Patient Empowerment Network on Vimeo.

Charise Gleason, a nurse practitioner, explains why tests such as bone marrow biopsy, FISH test and full-body imaging are considered essential for patients after a myeloma diagnosis.

Charise Gleason is a nurse practitioner specializing in myeloma and serves as the Advanced Practice Provider Chief at Winship Cancer Institute of Emory University. Learn more about Charise, here.

See More From INSIST! Myeloma

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Myeloma Targeted Therapy: Why Identifying Chromosomal Abnormalities is Key

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Key Considerations When Choosing Myeloma Treatment: What’s Available?


Transcript:

Charise:                       

The essential testing that a myeloma patient should undergo following a diagnosis is – obviously, you’ve had those diagnostic test labs, the 24-hour urine, some scans, but the specific things that we need are a bone marrow biopsy.

That includes cytogenetics and FISH, and we can talk a little bit more about that. You also want full-body imaging. We used to always use a skeletal survey, which was an X-ray of the long bones. But, really, the standard of care now is a whole-body scan.

So, depending on what your oncologist or your institution has, that would be a full-body CT scan, a PET-CT scan, or a full-body MRI. So, one of those tests is recommended. It’s not unusual if you have a PET. Like our institution, we use PET-CT. So, for a newly diagnosed patient, we’re also going to get an MRI of the spine for a further snapshot.

What we’re looking for with a full-body imaging is we want to make sure that there aren’t any lytic lesions.

So, with an X-ray, you have to have about 30 percent bone loss before it’s going to show up on an X-ray. So, those traditional X-rays that we used to use could actually miss an active lesion. So, in that diagnosis, we want to know that there is no active myeloma. And those other scans are going to be more specific to that.

So, the cytogenetics of a bone marrow biopsy are going to tell us more about the biology of the disease. So, cytogenetics actually grows out the pairs of cells. And so, that’s why that portion of the test can take a while to get back.

At our institution, it can take two to three weeks, because you’re actually growing out those cells to look at the chromosomes. And remember these are chromosomes, or genes, of the plasma cells. And so, we’re looking for those abnormalities that might be present. So, you think about it more for the biology of the disease.

When we’re looking at FISH, we’re also looking… That test shows a little bit different. It comes back quicker. It shows two different phases of cell changes.

And so, it will tell us about chromosomes as well. But do you have any additional chromosomes – so, that would make it a hyperdiploid narrow. It tells us if there’s a loss of a chromosome – so, you’re missing one, a hypodiploid. It also tells us about translocations – so, when you’ve had a piece of a chromosome change and go to another cell. And so, that, for instance, would be like that translocation t(11;14) or translocation t(4;14). So, it’s essential to have that testing to tell us about that, because it helps guide treatment. And as we talk more about targeted therapy, these things really can come into play.

Treatment Approaches in AML: Key Testing for Personalized Care

Treatment Approaches in AML: Key Testing for Personalized Care from Patient Empowerment Network on Vimeo.

When it comes to Acute Myeloid Leukemia (AML), genetic testing (or biomarker testing) is essential in helping to determine the best treatment approach for YOU. In this program, AML expert, Dr. Naval Daver reviews key decision-making factors, current AML treatments and emerging research for patients with AML.

Dr. Naval Daver is an Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. More about Dr. Daver here.

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See More From INSIST! AML

Related Resources:

 

How is Acute Myeloid Leukemia (AML) Treated?

 

Effective AML Combination Treatment: Pairing Old and New Therapies

 

Confused About AML Genetic Testing and Treatment? What You Need to Know

Transcript:

Katherine:                   

Welcome to INSIST! AML. A program focused on empowering patients to insist on better care. Today we’ll discuss the latest advances in AML, including the role of genetic testing and how this may affect treatment options. I’m Katherine Banwell, your host for today’s program. And joining me is Dr. Naval Daver. Welcome, Dr. Daver. Thank you so much for being here. Would you introduce yourself?

Dr. Daver:                    

Hello. Yeah. Thank you very much, Katherine. It’s a pleasure to join this discussion and meeting. I’m the Associate Professor in the Department of Leukemia at the MD Anderson Cancer Center. I focus on the treatment of acute myeloid leukemia and MDS, including the development of a number of clinical trials that are using targeted therapies and immune therapies for this disease. And with the great and dramatic progress, we’re seeing in acute myeloid leukemia; I think it is now more important than ever for patients to be aware of the options and be able to select the most appropriate therapy with their physicians.

Katherine:                   

Before we get into the discussion about AML, a reminder that this program is not a substitute for seeking medical advice. Please refer to your own healthcare team. Dr. Daver, I know the field of AML research is advancing rapidly. Would you give us an overview of the current treatment types in AML?

Dr. Daver:                    

There has been dramatic progress in the treatment of acute myeloid leukemia, especially in the last three years. We’ve had eight new drugs approved for the treatment of acute myeloid leukemia. The most progress I think that has happened so far is in the identification of particular molecular mutations and targeting those mutations with targeted therapies.

The mutations that are most important right now and have target options for FLT3 mutations, F-L-T-3, and the drugs that have been USDA-approved for this are an agent called Midostaurin, which is a first-generation FLT3 inhibitor and combination chemotherapy.

And then, more recently, another agent called Gilteritinib, as a single agent in relapse refractory FLT3 AML. The other mutational group that is also very important, and therapeutically needs to be checked, is IDHN1 and IDH2. And there are now two IDH inhibitors, IDH1 inhibitor, Ivosidenib, and IDH2 inhibitor, Enasidenib, both of which have been approved by the United States FDA for relapse patients with IDH1, IDH2 mutations. So, I think it’s really critical now to check for particular molecular mutations and to appropriately add the particular targeted therapy or select the particular targeted therapy in patients who have the mutation.

The other major area of advancement, and probably, if not the most important breakthrough that has happened, is the development of a new drug called Venetoclax. This is a BCL2 inhibitor. It’s new in AML, but in fact, it has been used for many years in CLL, which is chronic lymphocytic leukemia.

And this drug, in combination with Azacitidine in the frontline setting in older patients with AML who are not good candidates for intensive induction, has shown very high response rates, almost 70 percent CR-CRi, which is more than double of the 20 to 25 percent we were getting with Azacitidine alone.

And it’s now been approved by the US FDA and, in my opinion, and many of the experts really is the new standard of care and should be used in all older patients who are not good candidates for intensive chemotherapy given both the very high response rates, as well as now mature data showing significantly improved overall survival and a good tolerability.

So, there are many other breakthroughs. But I think these targeted agents, and Venetoclax, probably are the most impactful today.

And we’re focusing a number of new combinations building around this.  

Katherine:                   

What are common mutations in AML?

Dr. Daver:                    

Yeah. So, the most common mutation in AML is F-L-T-3, FLT3 mutation. This is both prognostically important mutation, presence of an FLT3 in a newly diagnosed AML, has been shown in many large publications by the German Cooperative Group, British Cooperative Group, our group, and others, is associated with an inferior survival.

Also, now, on top of that, it is also a therapeutically important mutation in addition to having negative prognostic value because the addition of FLT3 inhibitors seems to dilute, to a large extent, the negative prognostic value.

So, we believe that if we can identify FLT3 mutations at FLT3 inhibitors, we can definitely improve the outcome of those patients. The second most common is what we call NPM1 mutation, and that tends to occur with FLT3. About 55 percent of patients with an FLT3 mutation will have a coopering NPM1.

NPM1 is very interesting. With NPM1 mutation is present on it’s own without a FLT3, it’s actually associated with favorable outcome. It’s a favorable prognostic marker. However, if NPM1 is present with a FLT3, and especially if the FLT3 has a high quantity, high allelic load, then the NPM1 loses its favorable impact. So, now we’re kind of moving beyond just; do you have one mutation or not, which is what we thought 10 years ago, to; well, yes, you have this mutation, but what about the core-occurring mutation and even beyond. What about the burden, or what we call the variant allele frequency of that mutation?

So, for good or bad and I think it’s good in the end because it’s going to improve the patient outcomes, that we are getting more, more in-depth and there’s no longer quote, unquote, AML.

So, there’s a lot more granularity and analysis that is required even before starting treatment. And this is the thing that, in the community, we’re educating the doctors a lot, is that it’s okay to wait four to six days, especially if the patient does not have a very proliferative leukemia, to get the important bloodwork to identify the appropriate molecular and chromosome group.

So, that we can select the right treatment which will improve outcome rather than just rushing into standard treatment and missing a particular molecular chromosome group.

Katherine:                   

True. It might not be – the genetic testing might not be right for everyone.

Dr. Daver:                    

Right. Right.

Katherine:                   

What is genetic testing in AML?

Dr. Daver:                    

So, genetic testing in AML is basically what we call molecular profiling.

So, it’s looking at the presence of particular molecular mutations. For example, at MD Anderson, we do what we call 81 gene panel. So, this looks at 81 different genes for mutations in the bone marrow of newly diagnosed acute myeloid leukemia. Now, how did we come up with 81 genes? So, this was actually done by literature analysis and review of previously published preclinical and translational studies, and we basically selected all mutations that had been shown to occur in two percent or more of thousands of AML patients. And we found 81 such mutations. So, that any mutation that had a two percent or higher frequency in known published or public databases was included.

And that’s how we’re able to analyze for the mutation. So, it’s still possible that there may be some very rare mutations that are present, and those may be important for research. But they don’t change our treatment decision today. And so that’s what we call genetic profiling. Some people call it molecular mutation analysis. Some people call it next-generation sequencing.

But basically, this is looking for mutations in particular genes that are known to occur in AML. Now of those 81 genes; and some people do a 100 gene panel, some do 50, so those are variables; but among those, there are four or five that are most important: the FLT3, as we discussed, where we can use FLT3 inhibitors; IDH1 and two, because we can use IDH1 and IDH2 inhibitors; TP53 is a very important mutation because it has very high risk and adverse prognosis.

And there are now new drugs coming that may be very effective in TP53. So, we are checking for that. Those drugs are in trials, but the trials are showing very promising data and could be a great option if a patient is known to have a TP53.

Those drugs are Magrolimab, CD47 antibody, and APR-246. So, these are the four most important therapeutic mutations.

There are also some mutations that have prognostic value even though we cannot target them. These include mutations like RUNX1, DNMP3A, ASXL1.

One does not need to know the list. But the point is that these mutations may help determine whether a patient falls into intermediate-risk group or high-risk group, which then impacts the decision as to whether we need a stem cell transplant or not. So, it really is important to get this molecular profiling. It’s actually available in the United States commercially. And any clinic or hospital is able to actually order it. And insurance will cover it in 100 percent of the cases.

Katherine:                   

Wow, that’s great. What should – when should patients be tested, and how is testing done?

Dr. Daver:                   

Yeah. So, the basic testing for any suspected new acute leukemia is to get a bone marrow biopsy. That has to be done.

That should be done very quickly because all of the information that will be generated to make the treatment decision will come off the bone marrow biopsy.

Katherine:

What about retesting, Dr. Daver? Is that necessary?

Dr. Daver:                    

Yeah. So, retesting is necessary in – not for everything, I think.

But let’s say someone had treatment induction and relapsed a year later. So, we would definitely retest: 1) to confirm with the bone marrow’s relapsed AML, get the blast percentage because we need that before restarting treatment, so we know what was the starting point to know how the patients doing after treatment if he’s responding. 2) Molecular testing, for sure, should be repeated. We usually repeat the molecular testing such as FLT3, IDH1, IDH2, because there are drugs that can target these mutations in a relapse.

And more interestingly, we actually have published, and other groups have also published, that there are some patients who may not have those mutations at baseline but may actually acquire or have detectible mutations at relapse. So, if you don’t have FLT3 at baseline, your physician may assume that the FLT3 is not there, not do mutational testing. But in fact, that may not be true. So, it is important to retest about 15 percent, one five percent, in our publications can acquire a detectible FLT3. Which is critical because this could then change your treatment.

IDH1 and two are rarely lost or acquired, but we have seen a few five percent or so cases of that. So, it’s still better to check for that. And then TP53 we check for because now we have these new research clinical trials, phase one, two, that are showing some very encouraging activity in TP53. So, these are probably the main things to retest for.

There’s also some new clinical data emerging with a new drug called menin inhibitor that targets a particular chromosome abnormality, MLL rearrangement. This is again in a phase one setting, so the data may not be widely disseminated. But we’re seeing some very encouraging activity with menin inhibitors.  

And so, we are 100 percent checking for the MLL rearrangement chromosome, which can be done on FISH, or routine chromosome.

And if that is there then trying to get on one of the menin inhibitor trials, they’re opening about 25, 30 centers with different menin inhibitors, would be a very, very good option because we think these will be the next molecular or chromosome-targeted breakthrough in AML.

Katherine:                   

We’ve been discussing how molecular testing results lead to targeted therapy. How do targeted therapies work?

Dr. Daver:   

Targeted therapy means that we’re targeting a particular mutation. Now we may be targeting in different ways. So, some of the drugs, like FLT3 inhibitors, these are the most established and oldest targeted therapies in acute myeloid leukemia, been in development for about 18 to 20 years, work by blocking a particular receptor, the FLT3 receptor.

That receptor, when blocked, removes the growth and proliferation signal to the leukemia blast. And that receptor is much more preferentially and heavily expressed on the surface of the acute myeloid leukemia cell as compared to the normal, healthy myeloid or lymphoid cell. So, basically, we are shutting down the growth signals, resulting in eventual death of the leukemia blast and that’s how FLT3 inhibitors work. So, it’s a more of a direct activity resulting in cell death over a few days and quick action. On the other hand, we have what also is called targeted therapies but act very differently. These are IDH1, IDH2 inhibitors.

So, when you use an IDH1 or two inhibitor, they do go to the IDH1 and two receptor on the surface of the acute myeloid leukemia cell, but actually, they don’t result in the death of the cell. They actually cause what we call differentiation.

So, they promote that immature abnormal leukemia cell to undergo maturation and become a normal myeloid cell, which, over time, will die because normal cells have a finite lifespan, and they will die. As compared to leukemia blasts, which can live on much, much, much longer. And so, this process is called differentiation. So, FLT3 inhibitor, very different direct cell death. IDH inhibitor, very different from most maturation differentiation of immature cells to mature cells and takes longer. So, this is important clinically because with FLT3 inhibitors. We see responses quickly, one to two months. IDH inhibitors it takes longer, three to five months.

And so, targeted therapy is not one and all the same. You may be targeting a particular receptor, but the modality of action downstream may be very different.

Katherine:                   

What’s the treatment regimen for targeted therapies, and how long are patients treated with these types of therapies?

Dr. Daver:   

Yeah. I mean, that’s an area of big research. There’s no one field of answer yet for – and I don’t think there will be.

Of course, eventually. So, it really depends on; 1) What setting we’re using it in? Newly diagnosed, relapsed AML. In relapsed AML, with most targeted therapies, whether you’re use is a single agent, like FLT3, IDH1, IDH2, TP53, MLL-targeted agents, the goal is to get a patient to transplant.

Transplant, meaning allogeneic stem cell transplant using a sibling donor or a match-generated donor.

Because in relapsed AML without transplant, irrespective of the genetics and chromosomes, all relapsed AML have very poor outcome. The survival is only 20 percent or less without transplant.

If we can get a patient to transplant, we do have a good chance of long-term survival. So, the goal is transplant. And we usually use a targeted therapy for short, finite period, two to four months, to get a remission, get to transplant, hope that will cure the disease.

In front line, it’s quite different. We’re using induction chemotherapy with FLT3 inhibitors. In some research trials, we’re adding IDH1 and two inhibitors. We’re using Venetoclax, which is a kind of a targeted therapy.

Also, the BCL2 in combination with hypomethylating agents. And here, the targeted therapy is often used indefinitely. At least for one or two years. But in our approach and our guidelines, we continue the FLT3 inhibitor, IDH1 or two inhibitor or Venetoclax, as long as patient is tolerating it and does not have disease progression.

So, these are being used kind of similar to CML, chronic myeloid leukemia, where we use tyrosine kinase inhibitors or myelofibrosis, where you use jak inhibitors. They don’t cure the disease, but they continue to control the disease as long as you take them.

And in the end, we call this functional cure.

If somebody takes a FLT3 inhibitor and lives 20-plus years, semantically, he was never a cure, like an infection gets cured. But functionally, to me, he lived a normal life, and he was cured.

Dr. Daver:                    

And so, that’s how we’re using those inhibitors in the frontline setting different from the relapse setting.

Katherine:                   

How do these newer therapies differ from more traditional chemotherapy?

Dr. Daver:   

Yeah. Dramatically different. Completely different from traditional chemotherapy. So, to put it in more layman terms, traditional chemotherapy is like a nuclear bomb. Right? You – There’s a lot of things there in the marrow. You don’t know what’s good. You don’t know what’s bad. Blow it all up and hope that, when the new plants grow, the good ones grow and the bad ones were kill. And, in fact, this is true, to a large extent. Traditional chemotherapy, not to put it down, is actually been curative in a large population of AML for the last three decades. Our group and British MRC and Polish, and many groups have published up to 50 to 65 percent cure rates, especially in younger patients, below 65, with traditional chemotherapy.

So, this is not bad. People always get depressed with leukemia. But if you look at solid tumors, I mean, they have never achieved cure rates above 10 to 15 percent till the last decade or so. So, we were still getting 60, 65 percent cure rate. Two out of three.

So, traditional chemotherapy has done great work. But it was that approach. Just nuclear explosion. Take it all out, and hope good stuff comes.

Now the targeted therapy’s like a sniper. It’s actually looking for the particular leukemia cells and trying to take them out one by one with minimum collateral damage to your healthy bone marrow cells, which are important to produce red cells, platelets, white cells. So, guess what? There’s much less toxicity. You don’t see the hair loss with these agents. You don’t see the mouth sores and mucositis. GI complications are much less; infection risk is usually less.

Not to say they don’t have their own side effects. Unfortunately, even the targeted therapies have unique side effects. But, in general, those side effects are much less impactful in a negative quality-of-life way and much more manageable and tolerable. So – And, in the end of the day, they’re actually often more effective.

So, for example, with the FLT3 inhibitor, the study that was done with Gilterinib and Quizartinib, two very potent FLT3 inhibitors, was looking at a single-agent FLT3 inhibitor versus three-drug, high-intensity combination nuclear chemotherapy. And if I told this to any layperson, they would say, oh my God, that’s completely unfair comparison. You’re going to use three drugs, IV chemo, strong chemo, and compare it to one oral targeted pill. There’s no way the pill can be even equal, leave apart, win.

But guess what? The targeted therapy actually won. It not only was equal. It doubled the response rates, it reduced the toxicities and early mortality and led to improved overall survival, the gold standard. So, this shows that even though they are sniper, they can actually be much more effective with less toxicity. So, it’s a win-win. Better, tolerable, and more effective. Now the next stage within then decade, we think, it’s not one or the either, it’s really a combination. So, we’re reducing the dose of chemotherapy. So, we’re not making it as nuclear as it was. It’s still intense. But much more tolerable. And we’re compensating for that by adding the targeted therapy.

And, in fact, in the end, we expect much higher responses and survival with much better tolerability and lower early mortality. But I don’t think we’re at a stage where traditional chemotherapy is gone. Maybe 10, 12 years from now, as many more developments come, we’ll get there. But I think it still has a role, especially in the younger AML patients.

Katherine:                   

Dr. Daver, you mentioned the – some common side effects of chemotherapy. What about some of the newer therapies? Do they also have side effects?

Dr. Daver:                    

Yeah. Absolutely. I mean, every therapy we have in leukemia has a side effect. There’s no drug I can mention that is just devoid of them. Of course, some are less, and some are more. So, to be more specific, I think, for example, IDH1, IDH2 inhibitors, these are probably one of the most tolerable treatments we have in all of leukemia treatment. In general, they don’t cause much myelosuppression. Meaning, drop in blood counts. They don’t cause hair loss. They don’t cause mouth sores and GI upset in majority of people.

They’re always some patients who may. But what they can cause are two things: Number one, is they can cause what we call the differentiation syndrome.

And differentiation syndrome means the blasts that are going from the immature state to the mature state; in that process, they can cause an inflammatory reaction. And this can manifest with fever and cough, and chest pain, hypoxia. It’s something that’s actually very, very easily treatable, giving steroids for three or four days will take care of it. But many times, people were not aware of this. And so, often, we saw this was missed in the community.

So, that’s one specific example. With the FLT3 inhibitors, sometimes we see that they can cause more prolonged drop in blood counts, and count recovery can be delayed. Or we can sometimes see that they may cause some cardiac signals; increase in cardiac intervals. Again, something that, with close monitoring, bloodwork, keeping the electrolytes normal, can be managed. But I don’t want to go through the whole list. But the point is that there are specific and unique side effects that can be seen with particular targeted therapies.

And again, this is a learning curve where we have done these trials for eight to 10 years. So, we became familiar. But when the drug is approved, it’s a – it’s kind of a night-and-day situation in the community. They didn’t have the drug yesterday. They have it today. But there may not be any learning curve there. So, I think that’s where a lot of education and interaction with our colleagues is now coming into play.

But also, patients, I think, need to take this a little bit into their own hands, and also read about the label, read about the drug. So that, if they have side effects, if they actually ask their doctor and say, do you think this could be differentiation? I read about it. Yeah, most people will at least think about it. And I think this could be helpful to make sure that things are not missed. So, we do want patients to be more interactive and kind of  take things into their own hand. Because there are so many new drugs out there that their doctors may not be fully familiar yet.

Katherine:                   

Well, let’s talk about patient advocacy. What are some of the key tests that patients should ask for after they’ve been diagnosed?

Dr. Daver:                    

Yeah. Absolutely. So, I think the key things that patients should want to get the information is: 1) Knowing the bone marrow blasts.

I mean, that’s really basic. Just knowing what leukemia it is. What are the blast percentage? 2) Is, I think, chromosome analysis is very critical to get that information and to make sure we’re not missing acute promyelocytic leukemia, or core-binding factor leukemia, which have different treatments and very favorable outcomes, and would never, in general, never require a allogenic transplant. At least in majority of cases.

And 3), which is the one where we still see that it may sometimes not be available or be missed, is molecular testing.

I think it’s very critical to request molecular testing. And among molecular testing, especially FLT3, maybe IDH1 and IDH2, and TP53.

So, I think these are the most important data sets. Cytogenetics, key molecular mutations, bone marrow blasts, and confirmation of the type of leukemia before we embark on any treatment.

Katherine:                   

How can patients feel confident, do you think, in speaking up, and becoming a partner in their care?

Dr. Daver:   

Yeah. I mean, this is always a touchy area because physicians may feel that this is kind of encroaching on their territory or telling them what to do. And this is always a major challenge. I think when you go for the clinic visits, just to have a list of your questions written down and having them prepared and prioritizing them.

I always say, have your top-three questions ready.

We’ll try to do the others. But we’ll do the top three. And I think, when you have a new diagnosis of AML, the top three should be: what is the type of leukemia I have, and what are the bone marrow blasts? Number one. Do we have any chromosome and molecular information? Number two. And number three: Are there any specific treatments for my specific AML based on that chromosome molecular information? Or do we need additional information, and can we wait for that safely? I think these are the three very reasonable questions which, I think again, most leukemia experts will automatically be discussing this.

But, I think, for a patient, I think that’s important information to make sure they get before proceeding. If there’s time, the fourth question will be: Is – Are – Do we have a choice between high intensity, low intensity? And if we do, what are the pros and cons? In some cases, there may be a choice. In some cases, it may very clear that high intensity is the way to go, or low intensity is the way to go. But still, I think it’s often good to discuss that with your physician.

So, these are probably the four things one can bring up reasonably without the physician feeling that this is going to take forever, and I cannot discuss this. And then a lot of the AML treatment happens in-patient. So, there will be a lot of time for additional discussion. I tell my patients that, look, once we get the basics and the treatment decided, which is what we do in clinic, then you’ll be in the hospital most of the time. If it’s induction chemo for four weeks. Even if it’s Venetoclax, often they’re admitted for five to seven days, they will have more time then to discuss with the physician, the nurses, on a daily basis, and get more of the nitty-gritty.

Things like diet, exercise, lifestyle. Can I meet friends? I think you should not try to bring those things up right in the first visit. Because that may dilute the key information. So, I think staggering it, keeping in mind that many physicians are extremely busy, and getting that information in pieces over time, is probably productive for you and for the doctor.

Katherine:                   

With Covid-19 affecting all our lives right now, what should AML patients be considering at this time?

Dr. Daver:   

There’s a lot of guidelines on general approaches to managing things in COVID. And all of those guidelines heavily center, as we would think intuitively, on precautions.

Hand washing, minimizing contact, avoiding crowded places, trying to get treatment, potentially locally, if there are equivalent options available. We have not changed any of our frontline – we discuss this a lot every week in our faculty meeting.

This is discussed especially, as you know, because Houston currently is a major center affected heavily by COVID, and so, we have discussed whether we should move in a universal way to lower-intensity therapy for all patients. And we haven’t. And there’s pros and cons to that. When we do induction chemotherapy higher intensity, we, in fact, admit our patients for 28 days.

o, actually, even though it’s high intensity, the patient is more protected because they are in the room. Isolation rooms, sometimes. And they have minimum contact with outsiders. So, with COVID, actually, there’s very little opportunities or chances for them to get it. But the chemo is intensive. So, if they did get COVID, then it could be much more difficult or risky, or even fatal. On the other hand, low-intensity therapy is good because it’s low intensity and the risk of COVID, the frequency may or may not be changed; we don’t know. But the intensity we think could be lower because the immune system has not been suppressed.

However, low-intensity therapy very often is given outpatient. And so, then you have the benefit of lower intensity but the risk that you are going to be driving back and forth to the medical center, getting bloodwork, exposed to people in the waiting room, this and that. So, what we decided, after a lot of discussion among a big leukemia expert faculty in our group, was that we will still decide the optimum treatment based on the leukemia chromosome, molecular, age, fitness of the patient like we’ve always done.

And then we just have to try to encourage the patients to do as much precautions as possible. The other thing with the COVID, I think is very important is that, even though you may not be able to travel to your academic institution nearby because it’s harder to travel now, it’s still a good idea to try to get a consultation. We are doing a number of phone or email consultation, either directly with the patient, and even more frequently with their community doctor.

So, I get every day, four or five emails from academic even, and community physicians just saying, I have this patient, new AML, relapsed AML, whatever the case may be, here’s the mutation chromosome information, and I was going to do this. But the patient asked that I run this by one of my top academic colleagues. So, maybe MD Anderson. Some, I’m sure, are talking to Sloan. Some are, I know, are talking to Dana Farber. Cornell, whatever it may be. So, you can always request that. And maybe 100 percent of physicians may or may not do that.

And we’re seeing this collaboration actually. One of the positive things of COVID is we’re seeing these collaborations becoming better and better over time.

Katherine:                   

Oh, excellent. If a patient does need to go to clinic for a visit, what safety measures are in place?

Dr. Daver:   

Yeah. So, there’s a few things we’re doing in clinic is; one is we have staggered our clinics. So, instead of having everybody come at 9:00 or 10:00 a.m., and having 30 people in the waiting room, we really have more time slots.

And we ask people to come three of them at a time in the waiting room. We’re minimizing it three to five patients at most

Of course, there’s a lot of sanitization, dispensation units everywhere, encouraged to use those. The other important thing which, unfortunately, is a double-edged sword, is that we have had to minimize the number of friends, relatives, spouses, that can come with patients.

In fact, the policy at MD Anderson, like most cancer centers, is that nobody is allowed with the patient unless the patient is physically really impaired, as in wheelchair-bound or cannot go to the restroom. Of course, there are exceptions. But generally, I know, and I actually benefit a lot from it too, when patients have their family because the emotional support also helps our medical team to get information across. The patient may be sometimes stressed and forget things. So, what we’re doing more and more is doing phone calls.

So, what I would recommend is, as soon as doctor comes in, say, hey, doctor, can I call my daughter or my wife? I want her to listen to everything. Perfect. I don’t mind. There’s a speaker on. Good.

So, that helps with communication. But those are the big changes we have done from the clinic perspective. Still seems to be working relatively smoothly. We’re still seeing almost about the same number of patients in clinic that we were before COVID. And we have, fortunately, and knock on wood, not seen big numbers of leukemia patients with COVID. And we think the primary reason is because leukemia patients are just very cautious from the beginning. Even before COVID, they knew the risks, and we want them to continue that as much as possible.  

Katherine:

Dr. Daver, thank you so much for joining us today.

Dr. Daver:   

Thank you very much. Always a pleasure.

Katherine:

And thank you to all of our partners.

To learn more about AML and to access tools to help you become a more proactive patient, visit powerfulpatients.org. I’m Katherine Banwell – Thank you, Dr. Daver.

Is Myeloma Hereditary? The Facts.

Is Myeloma Hereditary? The Facts. from Patient Empowerment Network on Vimeo.

 Can myeloma be inherited? Dr. Irene Ghobrial, a myeloma expert and researcher, explains whether myeloma is hereditary.

Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Dr. Ghobrial specializes in multiple myeloma (MM) and Waldenström macroglobulinemia (WM), focusing on the precursor conditions of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma. More about this expert here.

See More From Fact of Fiction? Myeloma

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Transcript:

Patricia:

How about this one? “Myeloma is hereditary.”

Dr. Ghobrial:

It’s a very good question. So, it’s not hereditary specifically. However, there is a 2x increased risk in family members, and that goes back to that PROMISE study.

We are screening people who have first-degree relatives with myeloma. So, what does it mean? Why do I have a higher risk if I have a family member with myeloma? I recently saw a patient who – the patient had myeloma, the mother had myeloma, and the grandmother had myeloma, and you’re thinking, “Okay, there is something we’re inheriting.”

So, we don’t know. There are some susceptibility genes that we could potentially be inheriting, germ line, and we’ve done something called “germ line,” which means you have it from Mom and Dad, that can increase your risk. It could be other factors come in and we’re still trying to understand all of these factors. What are the genes that can increase your risk? Is there an immune factor that can increase your risk, and can we identify those early in the family members?

The Truth About MGUS

The Truth About MGUS from Patient Empowerment Network on Vimeo.

Is MGUS the same as smoldering myeloma? Myeloma expert, Dr. Irene Ghobrial, provides a detailed overview of MGUS, including the risk of progression.

Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Dr. Ghobrial specializes in multiple myeloma (MM) and Waldenström macroglobulinemia (WM), focusing on the precursor conditions of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma. More about this expert here.

See More From Fact of Fiction? Myeloma

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Transcript:

Patricia:

What about this one? “An MGUS diagnosis will lead to myeloma.”

Dr. Ghobrial:

Great question. So, let’s talk about MGUS in general. In the general population, once you’re over the age of 50, there’s a three percent change of having MGUS incidentally found, and that’s known from the big studies from Dr. Robert Kyle. Any of us walking around probably may have MGUS, and we don’t know.

We started recently a big study called the PROMISE study where we actually screen for the first time to look for myeloma – or, for MGUS – and the reason for that is we said, “You go screening for mammography with breast cancer, you go screening with a colonoscopy for colon cancer; we don’t screen for myeloma, which is an easy blood cancer with a blood test. Let’s screen for it.” So, that’s available online – promisestudy.org.

The other thing that we said is if you have MGUS, your chance of progression is only one percent per year. That’s very important to know. So, that means that in 10 years, you have a 10% chance of progression to myeloma. In 20 years, you have a 20% chance. So, if you’re 70 or 80, you may have something else that happens before you even develop myeloma or before you are at risk of myeloma.

However, that doesn’t mean that you don’t have the chance. You have a very small chance; it’s a precursor to myeloma, but it’s one of the biggest precursors to myeloma, so we always tell you, “Please go see your doctor, please do follow up with us because the one thing that’s important is we catch it early before it happens.” So, it does not always go to myeloma, but if we live for another 100 years, it may actually progress to myeloma because of the 1% chance per year.

Patricia:

How about this one? “MGUS and smoldering myeloma are the same.”

Dr. Ghobrial:

That’s not true. That’s a very important question. So, in general, MGUS is diagnosed as having less than 10% plasma cells and a small monoclonal protein, less than 3 grams, and you don’t have any organ damage.

Smoldering myeloma – and, the name says it; it’s almost myeloma, it has a higher chance of progressing to myeloma – in general, it’s about 10% per year, and usually, the bone marrow has more than 10% plasma cells. Now, you start telling me as a patient, “Well, if my bone marrow is nine percent, I’m MGUS, and if it’s 11%, I’m smoldering myeloma, that doesn’t make sense.” So, it’s correct. In general, those demarcations or numbers are more for us as physicians to talk to each other about what we’re calling rather than the patient themselves. The patient is a continuum.

So, you may move from MGUS to smoldering at a certain point, and it’s not really that extra percentage of bone marrow that moves you into the 10% risk. In general, again, smoldering myeloma, you have a higher chance of going to myeloma. So, I saw a patient recently who’s 30 who has smoldering myeloma. The chances of progressing to myeloma is 10% per year. In five years, you have a 50% chance.

You want to make sure that patient is followed up carefully, and you want to offer, potentially, clinical trials because we want to prevent progression. The hope in the future is you don’t want until you have lytic lesions, fractures in your bones, kidney failure, and then we treat. The hope is we treat you earlier and we can make a huge difference in that early intersection for myeloma.

Patricia:

It sounds like staying engaged with your care team is critical.

Dr. Ghobrial:

Absolutely, and I would say myeloma is a specialty field. Come and see a myeloma expert, wherever it is, even for a one-time consult, because it’s really complicated and it’s not a common disease, so it’s not something easy for everyone to know what to do with MGUS, what to do with smoldering, what to do with overt myeloma. I relax for the first time. All of these things are important, and just like you go and see the best specialist in anything, I would say care about your myeloma in a very specific way, ask your doctor questions, go online and look it up, and always ask an expert if you want to have a second opinion.

Why Should Myeloma Patients Visit the Dentist Frequently?

Why Should Myeloma Patients Visit the Dentist Frequently? from Patient Empowerment Network on Vimeo.

 Dr. Irene Ghobrial, a renowned myeloma specialist, explains why myeloma patients should be more vigilant about visiting the dentist.

Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Dr. Ghobrial specializes in multiple myeloma (MM) and Waldenström macroglobulinemia (WM), focusing on the precursor conditions of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma. More about this expert here.

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Transcript:

Patricia:

Dr. Ghobrial, let’s talk about some of the things that patients are concerned about when they come in about treatment side effects, and maybe some of those things aren’t true. Myeloma patients should visit the dentist more frequently.”

Dr. Ghobrial:

So, there is something about the bisphosphonates that we give patients, and they can cause – in a very rare number of patients – something called osteonecrosis of the jaw.

In the old days, when we didn’t know about that side effect, people would go get a root canal, come back, and have a big problem of osteonecrosis of the jaw with severe pain, and it doesn’t recover.

So, we’ve learned our lesson. We know very well that we hold Zometa or zoledronic acid if they’re getting any procedures. We make sure they don’t get surgical procedures – it doesn’t mean don’t get dental cleaning, please do the usual things for dental health, but don’t go into surgical procedures when you’re getting zoledronic acid – and we’re very careful with that.

We talk to our patients. Most dentists know about it, so I think this is something that in the old days, it was a problem. Now, we know how to medicate that.

The Truth About Myeloma Treatment Side Effects

The Truth About Myeloma Treatment Side Effects from Patient Empowerment Network on Vimeo.

 Managing myeloma treatment side effects can be overwhelming. Dr. Irene Ghobrial reviews common side effects and shares how life can go on, even while undergoing treatment for myeloma. Download the Program Resource Guide, here

Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Dr. Ghobrial specializes in multiple myeloma (MM) and Waldenström macroglobulinemia (WM), focusing on the precursor conditions of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma. More about this expert here.

See More From Fact of Fiction? Myeloma

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Myeloma Treatment Options: What’s Available?

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Transcript:

Patricia:                      

What are the common myeloma misconceptions about treatment side effects?

Dr. Ghobrial:              

I think the biggest thing is the loss of hair, the nausea, and fatigue, and to the point that I cannot travel, I cannot see my family, I’m gonna be so immunosuppressed. And again, that’s a huge misconception. Yes, there is toxicity for every drug. Even if you take aspirin, you have toxicity from it.

But, every drug has risks and benefits, and currently, the combinations we have are just impressive that they are well tolerated in general. I’m not saying there is no side effect – there is, for every different class of agents, there are, and you will go through those side effects with your doctor in detail – but in general, yes, you’re slightly immunosuppressed, you have to take care of it, and I said it yesterday to one of my patients – if someone is looking very sick in front of you, don’t go and hug them.

Christmas is around the corner, and we want to make sure people celebrate and enjoy life and enjoy the holidays with their family members.

Patricia:                      

Dr. Ghobrial, let’s talk about some of the things that patients are concerned about when they come in about treatment side effects, and maybe some of those things aren’t true. You tell me. Treatment side effects are unavoidable – we already talked a little bit about that. How about this one? “Myeloma patients should visit the dentist more frequently.”

Dr. Ghobrial:              

So, there is something about the bisphosphonates that we give patients, and they can cause – in a very rare number of patients – something called osteonecrosis of the jaw.

In the old days, when we didn’t know about that side effect, people would go get a root canal, come back, and have a big problem of osteonecrosis of the jaw with severe pain, and it doesn’t recover.

So, we’ve learned our lesson. We know very well that we hold Zometa or zoledronic acid if they’re getting any procedures. We make sure they don’t get surgical procedures – it doesn’t mean don’t get dental cleaning, please do the usual things for dental health, but don’t go into surgical procedures when you’re getting zoledronic acid – and we’re very careful with that.

We talk to our patients. Most dentists know about it, so I think this is something that in the old days, it was a problem. Now, we know how to medicate that.

Patricia:                      

Sure. How about this one? “Treatment causes increased risk for blood clots.”

Dr. Ghobrial:              

So, a couple of the drugs that we have – especially immunomodulators – can increase your risk for DVTs, blood clots, or pulmonary embolism, PE. So, the first thing we say is, “Let’s assess your baseline risk.

Are you someone who is at risk of clotting anyways?” Remember, myeloma also increases your risk of clotting, so you’re double. So, if you are at a high risk of clotting, then we would give the full anticoagulation. If you are not, then we would say aspirin is good enough to control that inflammation and endothelial damage that happens early on with therapy, and that can take care of it.

Patricia:                      

How about this one? “Side effects can be managed by diet and lifestyle.”

Dr. Ghobrial:              

So, I am a big believer that exercise and good, healthy living helps you in general. It makes your mood better, it makes you feel stronger, it gives you that energy because of the fatigue from the side effects, it helps with the dexamethasone because dex is a steroid, so you’re gonna be hungry, you’re gonna be eating more, and the on-and-off makes you fatigued and tired.

So, absolutely, diet and good healthy living – I’m not saying you have to go into extreme starvation and things like that. We say in general, be good, healthy living; exercise if you can.

Patricia:                      

What do you hear from your patients about side effects and treatments that they may think is true?

Dr. Ghobrial:              

I think neuropathy is very important, and we underestimate the neuropathy, so if you have numbness or tingling, tell your doctor.

That comes from Velcade; it comes from thalidomide when we used to use thalidomide, but it can happen in many patients who have an underlying amyloidosis and we did not diagnose it yet, or it can just happen as you go on from myeloma, rarely. So, tell your doctor about this.

I think the fatigue is very important to know about it because people suddenly change their life, and they want to know about that. I think the rashes that can happen with many of the drugs are very important to know about so that you’re not surprised when you get the rash. We know, for example, Revlimid can cause itching of the scalp, and that’s something that if we don’t tell the patients and they start going like this, then there is a problem.

So, it’s small things, but we want to let them know. We usually tell the patients everything, to a point of just going through all the side effects. It’s better to be aware of it, and then, if you get or not, at least you were aware.

Patricia:                      

Sure. How does one distinguish treatment side effects from comorbidities like fatigue?

Dr. Ghobrial:              

I think that’s important, and again, talking to your doctor is very important. Keeping a diary on the side is very important because you may have had some of those problems, and that could be from myeloma before you even started the drugs, and making sure that we know what’s from myeloma, what’s from your thyroid issue, what’s from your lung problems if you have asthma or COPD, what’s your diabetes if you have that or your other medications, from what are you doing with those medications.

I think that’s why when you start therapy, we tell you, “Try not to take too many other medications that we don’t know about, herbal medicines and other things, because then we don’t know what are the side effects and what’s causing what.”

Patricia:                      

Sure. You mentioned neuropathy. Let’s talk a little bit about what that is.

Dr. Ghobrial:              

So, neuropathy can come in different ways, but the most common one is numbness and tingling that you have in your tips of toes and tips of your fingers, and that can happen from medications, as we said, or from the underlying myeloma or amyloidosis. It can be painful, and we’re careful that if you have this, tell your doctor because if it get worse and worse, it’s very hard for us to reverse neuropathy, so just always tell us because we can stop the drug, we can decrease the dose rather than having you go through it.

Addressing Clinical Trial Misconceptions: The Facts

Addressing Clinical Trial Misconceptions: The Facts. from Patient Empowerment Network on Vimeo.

Dr. Irene Ghobrial, a myeloma specialist and researcher, dispels common myths associated with clinical trials, including a review of each phase of the clinical trial process.

Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Dr. Ghobrial specializes in multiple myeloma (MM) and Waldenström macroglobulinemia (WM), focusing on the precursor conditions of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma. More about this expert here.

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Transcript:

Patricia:

Sure. What about clinical trials? What common misconceptions do you hear from patients enrolling in trials?

Dr. Ghobrial:

There’s a lot of misconceptions, and it’s unfortunate. I would say I would absolutely go on a trial if I can. I’m a believer in clinical trials because they’re the way forward to bring in new therapies and new options. I think a lot of people think that we’re experimenting on them when we’re doing clinical trials, meaning that it’s first in human, meaning it’s the first time we try this drug, and I would say that most of our clinical trials are not first in human.

They’re not the very first time we’ve tried them. Likely, those are drugs we’ve tried, we know the side effects, we know the toxicity, but it’s the first time we’ve put it in a different combination or it’s the first time we’ve put it in a specific subset of patients to look at response or at overall survival.

Most of the trials – so, before you decide “Oh, it’s a trial,” just think – is this a phase 1, a phase 2, or a phase 3? Phase 1 are usually that first time that we try in a population. Phase 2 are usually we know already what happens, we know the toxicity, we’re bringing it to look at the response rate in general or the survival, and then, phase 3s are the bigger studies, going to the FDA for approval.

The second thing is you want to think about is there a placebo arm in it. Most of my patients really worry about “Oh my God, you’re gonna give me the placebo,” and I’m like, “No, we don’t have a placebo arm in this trial. You’re taking the drug that we tell you about.” So again, depending on the trial – read it carefully – there may be a placebo arm, but in most of them, it’s not a placebo arm.

So, I would personally go ask the doctor every time, “So, you’re talking about standard of care. What else do you have? Do you have clinical trial options or not? What’s new?” Almost every single new drug that we’re gonna get approved in the next 5-10 years from now is what we have today in clinical trials. It would be cool to try and get access to those earlier.

Patricia:

So, there’s a significant amount of vetting that goes on before clinical trials are actually in process on humans.

Dr. Ghobrial:              

Oh, absolutely.

Myeloma Treatment Options: What’s Available?

Myeloma Treatment Options: What’s Available? from Patient Empowerment Network on Vimeo

Renowned myeloma researcher, Dr. Irene Ghobrial, provides an overview of current treatment options for myeloma, including an explanation of the now commonly used four-drug regimen.

Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Dr. Ghobrial specializes in multiple myeloma (MM) and Waldenström macroglobulinemia (WM), focusing on the precursor conditions of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma. More about this expert here.

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Transcript:

Patricia:

Let’s get an overview of available myeloma treatments.

Dr. Ghobrial:

Oh, boy. Okay, how long do we have here? It depends. The moment I see a patient – and again, maybe we can start with smoldering myeloma because that’s an area I’m really excited about.

If you have asymptomatic disease, it does not mean you have to watch and wait until you fall apart, until you have bone lesions, until you have anemia. We want to see those patients early because we have a lot of clinical trials, and potentially, the cure may actually be in an earlier precursor session when we treat you earlier before you have the disease.

But, the standard of care is when you have symptoms – anemia, hypercalcemia, lytic lesions, and renal failure, or other things like 60% plasma cells – we say you have active multiple myeloma, and in that case, we start saying, “Well, are you a transplant candidate or not?” In the old days, it used to be by age, but now, we say age is just a number, so it really depends on if you have good organ function, are you in an active good state, do you have good lungs, good heart, are you willing to take the transplant, because now, there’s a big discussion whether we should transplant patients or not.

And then, at the end of the day, we’re starting to actually blur that, saying that most of our treatments are almost identical, whether you are old or young, whether you’re a transplant candidate or not. It depends on frailty. Can you tolerate this treatment or not? Maybe a few years ago, we used to say a three-drug regimen is the best way to go.

Now, most of us are starting to say four-drug regimen up front is the way to go, which is an antibody – currently, it’s daratumumab – a proteasome inhibitor – it could be bortezomib or carfilzomib – an immunomodulator – likely, this is lenalidomide – and then, dexamethasone. That’s sort of the option that we have right now, at least in the U.S.

If you go to Europe, you’ll find us using different drugs, like thalidomide or other things, but most of us are thinking of a four-drug regimen to think of our up-front myeloma treatment to get you the best remission, eventually MRD-negative disease, and then we talk about transplant or no transplant, and then, of course, we talk about maintenance.

We want to keep everyone on maintenance therapy; the question is how long, which maintenance, do we use one drug or not? So, there is a lot to be discussed in treatment of myeloma, and that’s the beauty of it. It’s truly an art and science together. It’s not just “Here’s a combination because you have this treatment.” We really personalize therapy for you.

We look at your cytogenetics, your FISH. We say you have high-risk cytogenetics or not, you’re young or not, you have good organ function or not.

There are so many things that we put in consideration when we come up with a treatment plan for a patient.

Fact or Fiction? Myeloma Treatment & Side Effects

Fact or Fiction? Myeloma Treatment & Side Effects from Patient Empowerment Network on Vimeo.

When it comes to online myeloma information, how do you separate fact from fiction? Dr. Irene Ghobrial shares facts about current myeloma treatments, common side effects and emerging research. Download the Program Resource Guide, here

Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Dr. Ghobrial specializes in multiple myeloma (MM) and Waldenström macroglobulinemia (WM), focusing on the precursor conditions of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma. More about this expert here.

See More From Fact of Fiction? Myeloma

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Transcript:

Patricia:

Welcome to Fact or Fiction: Multiple Myeloma Treatment and Side Effects. Today, we’ll review common misconceptions about myeloma. I’m Patricia Murphy, your host for today’s program. Joining me is Dr. Irene Ghobrial. Dr. Ghobrial, why don’t you introduce yourself?

Dr. Ghobrial:

My name is Irene Ghobrial. I’m a professor of medicine at Dana-Farber Cancer Institute, Harvard Medical School.

Patricia:

Great, thanks so much. Before we get started, just a reminder: This program is not a substitute for medical advice, so please consult your care team before making any treatment decisions. Okay, Dr. Ghobrial, let’s get started.

Let’s talk about some of the things, first, that we hear from patients. You tell me whether or not this is fact or fiction. Here’s one: “There are a number of treatment options for myeloma.”

Dr. Ghobrial:

Fact. It’s amazing because I trained in the old days – and, this shows you how old I am – when we only had bad chemotherapy: Vincristine, Adriamycin, and dex. None of you would even know about it.

Then, we had had high-dose dexamethasone, and that was it, and then we had stem cell transplant, and that’s all we had until suddenly, we had thalidomide, lenalidomide, bortezomib, carfilzomib, ixazomib, and you think about it, we are now in an era where we have 15-20 new drugs, we have another 15-20 coming up, we have an amazing time to completely cure myeloma in the future, and that’s just an exciting time to see that happening in the last 15 years of our lifetime, when patients were living three years, when we had – I remember five percent complete remission rate.

Now, we expect that all of our patients should get into a deep remission into potentially MRD-negative disease, and that’s just the beauty of how myeloma has changed completely.

Patricia:

Well, you’ve already busted our second myth, I guess, that there is no cure for myeloma.

Dr. Ghobrial:

That’s correct. There is no cure for myeloma, but there is a long remission, and the question is if someone lives for 20, 25, 30 years without evidence of myeloma and they die from something else, it’s a step forward. I would love to see us say to a patient, “You are cured,” but until then, we’re getting longer and longer remissions.

Patricia:

How about this one? “Only blood relatives can be donors for bone marrow or stem cell transplant.”

Dr. Ghobrial:

That’s not correct at all. If we think about it, what is stem cell transplant? There are two types. There’s something called autologous stem cell transplant, meaning it’s from myself, so that means that I’m taking my own stem cells, and the whole idea of that autologous transplant is basically high-dose chemotherapy.

So let’s take your own cells before we give you that high-dose melphalan, give the chemo, and then give them back to you, so that you’re not with low blood counts for two weeks, four weeks, you’re only with low blood counts for a couple of weeks. So, that’s autologous transplant; that means I’m giving my own stem cells to myself.

Allogeneic stem cell transplant, which we rarely do now in myeloma, is from another person, and that could be from a relative, but also can be from unrelated donors if they are matching us, but that’s very few cases.

Patricia:

Let’s get an overview of available myeloma treatments.

Dr. Ghobrial:

Oh, boy. Okay, how long do we have here? It depends. The moment I see a patient – and again, maybe we can start with smoldering myeloma because that’s an area I’m really excited about.

If you have asymptomatic disease, it does not mean you have to watch and wait until you fall apart, until you have bone lesions, until you have anemia. We want to see those patients early because we have a lot of clinical trials, and potentially, the cure may actually be in an earlier precursor session when we treat you earlier before you have the disease.

But, the standard of care is when you have symptoms – anemia, hypercalcemia, lytic lesions, and renal failure, or other things like 60% plasma cells – we say you have active multiple myeloma, and in that case, we start saying, “Well, are you a transplant candidate or not?” In the old days, it used to be by age, but now, we say age is just a number, so it really depends on if you have good organ function, are you in an active good state, do you have good lungs, good heart, are you willing to take the transplant, because now, there’s a big discussion whether we should transplant patients or not.

And then, at the end of the day, we’re starting to actually blur that, saying that most of our treatments are almost identical, whether you are old or young, whether you’re a transplant candidate or not. It depends on frailty. Can you tolerate this treatment or not? Maybe a few years ago, we used to say a three-drug regimen is the best way to go.

Now, most of us are starting to say four-drug regimen up front is the way to go, which is an antibody – currently, it’s daratumumab – a proteasome inhibitor – it could be bortezomib or carfilzomib – an immunomodulator – likely, this is lenalidomide – and then, dexamethasone. That’s sort of the option that we have right now, at least in the U.S.

If you go to Europe, you’ll find us using different drugs, like thalidomide or other things, but most of us are thinking of a four-drug regimen to think of our up-front myeloma treatment to get you the best remission, eventually MRD-negative disease, and then we talk about transplant or no transplant, and then, of course, we talk about maintenance.

We want to keep everyone on maintenance therapy; the question is how long, which maintenance, do we use one drug or not? So, there is a lot to be discussed in treatment of myeloma, and that’s the beauty of it. It’s truly an art and science together. It’s not just “Here’s a combination because you have this treatment.” We really personalize therapy for you.

We look at your cytogenetics, your FISH. We say you have high-risk cytogenetics or not, you’re young or not, you have good organ function or not.

There are so many things that we put in consideration when we come up with a treatment plan for a patient.

Patricia:

We’ve been talking a little bit about what patients believe when they come in, some of the things they’re thinking about. What else do you hear from patients that you either have to correct or affirm when they come into your office?

Dr. Ghobrial:

A lot of things. I think the first thing is, of course, they say myeloma is fatal, and they’re so scared, and absolutely, I understand that, but the median survival has become so much better, so much longer. There is a lot of hope, enthusiasm, and excitement right now with the treatments we have. The second thing is most of our treatments are not your typical chemotherapy, so unlike breast cancer or other cancers where you lose your hair, you’re throwing up, you cannot work, you have to take time off, most of our drugs now, people are working full-time, they’re active, you don’t lose your hair, so probably, no one has to know unless you tell them.

And, I think that’s something important for a patient to think about. It’s their own personal life, and not having to interrupt that. I think that’s very unique. So, these are a couple things that, as they come in, that anxiety of “Oh my God, I have cancer,” and then, taking a deep breath and saying, “Now, how do I handle this situation?”

Patricia:

Sure. What about clinical trials? What common misconceptions do you hear from patients enrolling in trials?

Dr. Ghobrial:

There’s a lot of misconceptions, and it’s unfortunate. I would say I would absolutely go on a trial if I can. I’m a believer in clinical trials because they’re the way forward to bring in new therapies and new options. I think a lot of people think that we’re experimenting on them when we’re doing clinical trials, meaning that it’s first in human, meaning it’s the first time we try this drug, and I would say that most of our clinical trials are not first in human.

They’re not the very first time we’ve tried them. Likely, those are drugs we’ve tried, we know the side effects, we know the toxicity, but it’s the first time we’ve put it in a different combination or it’s the first time we’ve put it in a specific subset of patients to look at response or at overall survival.

Most of the trials – so, before you decide “Oh, it’s a trial,” just think – is this a phase 1, a phase 2, or a phase 3? Phase 1 are usually that first time that we try in a population. Phase 2 are usually we know already what happens, we know the toxicity, we’re bringing it to look at the response rate in general or the survival, and then, phase 3s are the bigger studies, going to the FDA for approval.

The second thing is you want to think about is there a placebo arm in it. Most of my patients really worry about “Oh my God, you’re gonna give me the placebo,” and I’m like, “No, we don’t have a placebo arm in this trial. You’re taking the drug that we tell you about.” So again, depending on the trial – read it carefully – there may be a placebo arm, but in most of them, it’s not a placebo arm.

So, I would personally go ask the doctor every time, “So, you’re talking about standard of care. What else do you have? Do you have clinical trial options or not? What’s new?” Almost every single new drug that we’re gonna get approved in the next 5-10 years from now is what we have today in clinical trials. It would be cool to try and get access to those earlier.

Patricia:

So, there’s a significant amount of vetting that goes on before clinical trials are actually in process on humans.

Dr. Ghobrial:              

Oh, absolutely.

Patricia:                      

What are the common myeloma misconceptions about treatment side effects?

Dr. Ghobrial:              

I think the biggest thing is the loss of hair, the nausea, and fatigue, and to the point that I cannot travel, I cannot see my family, I’m gonna be so immunosuppressed. And again, that’s a huge misconception. Yes, there is toxicity for every drug. Even if you take aspirin, you have toxicity from it.

But, every drug has risks and benefits, and currently, the combinations we have are just impressive that they are well tolerated in general. I’m not saying there is no side effect – there is, for every different class of agents, there are, and you will go through those side effects with your doctor in detail – but in general, yes, you’re slightly immunosuppressed, you have to take care of it, and I said it yesterday to one of my patients – if someone is looking very sick in front of you, don’t go and hug them.

Christmas is around the corner, and we want to make sure people celebrate and enjoy life and enjoy the holidays with their family members.

Patricia:                      

Dr. Ghobrial, let’s talk about some of the things that patients are concerned about when they come in about treatment side effects, and maybe some of those things aren’t true. You tell me. Treatment side effects are unavoidable – we already talked a little bit about that. How about this one? “Myeloma patients should visit the dentist more frequently.”

Dr. Ghobrial:              

So, there is something about the bisphosphonates that we give patients, and they can cause – in a very rare number of patients – something called osteonecrosis of the jaw.

In the old days, when we didn’t know about that side effect, people would go get a root canal, come back, and have a big problem of osteonecrosis of the jaw with severe pain, and it doesn’t recover.

So, we’ve learned our lesson. We know very well that we hold Zometa or zoledronic acid if they’re getting any procedures. We make sure they don’t get surgical procedures – it doesn’t mean don’t get dental cleaning, please do the usual things for dental health, but don’t go into surgical procedures when you’re getting zoledronic acid – and we’re very careful with that.

We talk to our patients. Most dentists know about it, so I think this is something that in the old days, it was a problem. Now, we know how to medicate that.

Patricia:                      

Sure. How about this one? “Treatment causes increased risk for blood clots.”

Dr. Ghobrial:              

So, a couple of the drugs that we have – especially immunomodulators – can increase your risk for DVTs, blood clots, or pulmonary embolism, PE. So, the first thing we say is, “Let’s assess your baseline risk.

Are you someone who is at risk of clotting anyways?” Remember, myeloma also increases your risk of clotting, so you’re double. So, if you are at a high risk of clotting, then we would give the full anticoagulation. If you are not, then we would say aspirin is good enough to control that inflammation and endothelial damage that happens early on with therapy, and that can take care of it.

Patricia:                      

How about this one? “Side effects can be managed by diet and lifestyle.”

Dr. Ghobrial:              

So, I am a big believer that exercise and good, healthy living helps you in general. It makes your mood better, it makes you feel stronger, it gives you that energy because of the fatigue from the side effects, it helps with the dexamethasone because dex is a steroid, so you’re gonna be hungry, you’re gonna be eating more, and the on-and-off makes you fatigued and tired.

So, absolutely, diet and good healthy living – I’m not saying you have to go into extreme starvation and things like that. We say in general, be good, healthy living; exercise if you can.

Patricia:                      

What do you hear from your patients about side effects and treatments that they may think is true?

Dr. Ghobrial:              

I think neuropathy is very important, and we underestimate the neuropathy, so if you have numbness or tingling, tell your doctor.

That comes from Velcade; it comes from thalidomide when we used to use thalidomide, but it can happen in many patients who have an underlying amyloidosis and we did not diagnose it yet, or it can just happen as you go on from myeloma, rarely. So, tell your doctor about this.

I think the fatigue is very important to know about it because people suddenly change their life, and they want to know about that. I think the rashes that can happen with many of the drugs are very important to know about so that you’re not surprised when you get the rash. We know, for example, Revlimid can cause itching of the scalp, and that’s something that if we don’t tell the patients and they start going like this, then there is a problem.

So, it’s small things, but we want to let them know. We usually tell the patients everything, to a point of just going through all the side effects. It’s better to be aware of it, and then, if you get or not, at least you were aware.

Patricia:                      

Sure. How does one distinguish treatment side effects from comorbidities like fatigue?

Dr. Ghobrial:              

I think that’s important, and again, talking to your doctor is very important. Keeping a diary on the side is very important because you may have had some of those problems, and that could be from myeloma before you even started the drugs, and making sure that we know what’s from myeloma, what’s from your thyroid issue, what’s from your lung problems if you have asthma or COPD, what’s your diabetes if you have that or your other medications, from what are you doing with those medications.

I think that’s why when you start therapy, we tell you, “Try not to take too many other medications that we don’t know about, herbal medicines and other things, because then we don’t know what are the side effects and what’s causing what.”

Patricia:                      

Sure. You mentioned neuropathy. Let’s talk a little bit about what that is.

Dr. Ghobrial:              

So, neuropathy can come in different ways, but the most common one is numbness and tingling that you have in your tips of toes and tips of your fingers, and that can happen from medications, as we said, or from the underlying myeloma or amyloidosis. It can be painful, and we’re careful that if you have this, tell your doctor because if it get worse and worse, it’s very hard for us to reverse neuropathy, so just always tell us because we can stop the drug, we can decrease the dose rather than having you go through it.

31:59

Patricia:                      

What about this one? “An MGUS diagnosis will lead to myeloma.”

Dr. Ghobrial:     

Great question. So, let’s talk about MGUS in general. In the general population, once you’re over the age of 50, there’s a three percent change of having MGUS incidentally found, and that’s known from the big studies from Dr. Robert Kyle. Any of us walking around probably may have MGUS, and we don’t know.

We started recently a big study called the PROMISE study where we actually screen for the first time to look for myeloma – or, for MGUS – and the reason for that is we said, “You go screening for mammography with breast cancer, you go screening with a colonoscopy for colon cancer; we don’t screen for myeloma, which is an easy blood cancer with a blood test. Let’s screen for it.” So, that’s available online – promisestudy.org.

The other thing that we said is if you have MGUS, your chance of progression is only one percent per year. That’s very important to know. So, that means that in 10 years, you have a 10% chance of progression to myeloma. In 20 years, you have a 20% chance. So, if you’re 70 or 80, you may have something else that happens before you even develop myeloma or before you are at risk of myeloma.

However, that doesn’t mean that you don’t have the chance. You have a very small chance; it’s a precursor to myeloma, but it’s one of the biggest precursors to myeloma, so we always tell you, “Please go see your doctor, please do follow up with us because the one thing that’s important is we catch it early before it happens.” So, it does not always go to myeloma, but if we live for another 100 years, it may actually progress to myeloma because of the 1% chance per year.

Patricia:                      

How about this one? “MGUS and smoldering myeloma are the same.”

Dr. Ghobrial:              

That’s not true. That’s a very important question. So, in general, MGUS is diagnosed as having less than 10% plasma cells and a small monoclonal protein, less than 3 grams, and you don’t have any organ damage.

Smoldering myeloma – and, the name says it; it’s almost myeloma, it has a higher chance of progressing to myeloma – in general, it’s about 10% per year, and usually, the bone marrow has more than 10% plasma cells. Now, you start telling me as a patient, “Well, if my bone marrow is nine percent, I’m MGUS, and if it’s 11%, I’m smoldering myeloma, that doesn’t make sense.” So, it’s correct. In general, those demarcations or numbers are more for us as physicians to talk to each other about what we’re calling rather than the patient themselves. The patient is a continuum.

So, you may move from MGUS to smoldering at a certain point, and it’s not really that extra percentage of bone marrow that moves you into the 10% risk. In general, again, smoldering myeloma, you have a higher chance of going to myeloma. So, I saw a patient recently who’s 30 who has smoldering myeloma. The chances of progressing to myeloma is 10% per year. In five years, you have a 50% chance.

You want to make sure that patient is followed up carefully, and you want to offer, potentially, clinical trials because we want to prevent progression. The hope in the future is you don’t want until you have lytic lesions, fractures in your bones, kidney failure, and then we treat. The hope is we treat you earlier and we can make a huge difference in that early intersection for myeloma.

Patricia:                      

It sounds like staying engaged with your care team is critical.

Dr. Ghobrial:              

Absolutely, and I would say myeloma is a specialty field. Come and see a myeloma expert, wherever it is, even for a one-time consult, because it’s really complicated and it’s not a common disease, so it’s not something easy for everyone to know what to do with MGUS, what to do with smoldering, what to do with overt myeloma. I relax for the first time. All of these things are important, and just like you go and see the best specialist in anything, I would say care about your myeloma in a very specific way, ask your doctor questions, go online and look it up, and always ask an expert if you want to have a second opinion.

Patricia:                      

Sure. How about this one? “Myeloma is hereditary.”

Dr. Ghobrial:              

It’s a very good question. So, it’s not hereditary specifically. However, there is a 2x increased risk in family members, and that goes back to that PROMISE study.

We are screening people who have first-degree relatives with myeloma. So, what does it mean? Why do I have a higher risk if I have a family member with myeloma? I recently saw a patient who – the patient had myeloma, the mother had myeloma, and the grandmother had myeloma, and you’re thinking, “Okay, there is something we’re inheriting.”

So, we don’t know. There are some susceptibility genes that we could potentially be inheriting, germ line, and we’ve done something called “germ line,” which means you have it from Mom and Dad, that can increase your risk. It could be other factors come in and we’re still trying to understand all of these factors. What are the genes that can increase your risk? Is there an immune factor that can increase your risk, and can we identify those early in the family members?

Patricia:                      

What about preventing progression from smoldering? Is there anything patients can do?

Dr. Ghobrial:              

I would say enroll on the PCROWD. Study PCROWD is empowering patients themselves to go online. You can look it up – PCrowd with Dana-Farber – so, precursor crowdsourcing.

This is a study where anyone who has MGUS or smoldering myeloma can tell us about their data – so, their clinical information – tell us about their samples – so, give us their samples whenever they’re going to get their peripheral blood or their bone marrow – and by doing that, we can look at 1,000-3,000 people, put it all together, and hopefully give you very soon the answer of what causes progression, what are the specific markers genomically and immune that can predict progression, and can we target them?

Can we develop therapy for you specifically as a smoldering patient and not use the same drugs as myeloma, but target it for one specific patient for one specific operation?

Patricia:                      

When patients come into your office, they’re learning a lot of new things. Are there terms that are confusing to patients that you need to define for them?

Dr. Ghobrial:              

Absolutely. I think a lot of those terms are very hard. The words “complete remission” – was that a cure or not? It’s not.

We decrease all of your M spike, we decrease your plasma cells to zero, but it doesn’t mean that we’ve cured you. I think progression is very important. We use certain numbers. A 25% increase in your M spike or a 0.5-gram increase – even monoclonal protein is important to understand, that that’s the antibody that your plasma cells are secreting.

So, absolutely, there are so many words that could be very daunting for any patient to go through all of this. I think having an advocate with you – don’t go on your own because there’s so much information you’re getting that first time. I personally think if patients are recording us or taking notes, that’s perfectly fine because you go back and think about it, and you want to make sure that the information is clear.

So, it’s a lot of information to take in, especially if you’re not in the medical field, and I would encourage patients to ask questions, take notes, think about it a lot.

Patricia:                      

Tell me what an M spike is.

Dr. Ghobrial:    

So, an M spike – a monoclonal spike – is the protein – the antibodies. So, plasma cells are actually antibody-secreting cells, so they secrete the antibody, it goes in the blood, and when you have a lot of it from the same type of cell, they’re monoclonal, so they’re all the same IgG kappa – IgG kappa because they came all from that same kind of plasma cells.

And, when we run a specific gel, called serum protein electrophoresis, all of those antibodies will run in one area, and they will do a spike instead of going into a bigger area, where we call it polyclonal. So, that tiny little spike, which is a very high level of all of them coming together, we can measure it, and we can say, “Your monoclonal spike is 3 grams per deciliter.” If you don’t have all of them the same type of protein, they will just go around in one big area – big lump, basically, on that electrophoresis, and they will not come out as a spike. So, that’s monoclonal spike. 40:44

Patricia:                      

And, what are some reliable source of information for myeloma? The world wide web is vast.

Dr. Ghobrial:              

Yeah, and it’s unfortunate. So, there is so much information, and you can get lost, and you can also get misinformation. I think some of the big foundations are very important So, I would say the Multiple Myeloma Research Foundation, the International Myeloma Foundation, the Leukemia and Lymphoma Society, and of course, if you go to clinicaltrials.gov, you will find that information, and you’ll find a lot of the clinical trials. But again, ask your doctor. Ask the experts.

Patricia:

There are a lot of online forums – again, we talked about how vast the internet is. How can a patient identify misinformation online? What are some clues?

Dr. Ghobrial:              

That’s a hard one. I would say again, print it and take it to your doctor. Tell him, “Does that make sense? I’ve read this.” This is where you really need to do your research and go to the sites that you have confidence in so that you’re not lost in the middle of so much misinformation.

Patricia:                      

Do you have patients come in and say things to you that you just have to say, “Whoa, that’s just not accurate”?

Dr. Ghobrial:              

Yeah, but again, this is part of the discussion. I personally think every question is a good question. Even if it sounds completely ridiculous, ask it. That’s why we’re here. We’re here to tell you, “This is right, this is wrong, this one I don’t know, I’m not so sure,” and that’s okay. It’s part of the discussion.

Patricia:                      

Before we finish up, let’s get your take on the future of myeloma. What are you seeing on the horizon?

Dr. Ghobrial:              

Oh, a lot, and I hope I live long enough to see all of the amazing things. I truly think that we will cure myeloma. I think we should treat patients early. That’s an absolute change.

I think immunotherapy is coming in, CAR-T, bispecific antibodies. We will harness our immune system to kill myeloma, and I think there’s so much to be done there. I think precision medicine is very important. The first study is from MMRF [Multiple Myeloma Research Foundation] coming out now, genotyping, asking the questions “Which mutations do you have?”, and then putting them into different buckets so you can understand which disease should be treated with which drug.

We always say we know there is different subtypes of myeloma, then we treat you the same way, so let’s stop doing that, let’s do precision medicine, let’s individualize treatment specifically for you. So, I think that’s another big thing. So, in the future, there will be so many options. The hope is truly we’ll cure myeloma, we diagnose it early, we screen for it, we diagnose it early, and we prevent it from even causing one lytic lesion for a patient. 41:52

Patricia:                      

Dr. Ghobrial, let’s end by talking about why you’re so hopeful about the future of myeloma.

Dr. Ghobrial:              

Well, again, I trained – and, I said that 15 years ago – at Mayo Clinic, where we only had few drugs, when the survival of myeloma was three to five years, when we saw patients having severe fractures and severe pain, and now, we look at it, and it’s only 15 years in our lifetime, and we look at it that myeloma is a completely different disease.

We can diagnose it early – in fact, we’re thinking of screening them early – we can make a huge difference in all of the comorbidities, but the most important thing is we have so many amazing drugs that we’re using together to get an amazing, complete remission, MRD-negative disease, and then, in the next 5-10 years, I think we will change, again, immunotherapy with CAR-T. We will have precision medicine and immunotherapy to completely change how we treat myeloma. So, I am extremely hopeful and extremely excited for our patients.

Patricia:                      

So, how do you talk to your patients about this hope? I would imagine that when they come in, they’re pretty terrified about what’s going on.

Dr. Ghobrial:              

Absolutely. Again, the first thing is you want to say, “Yes, you have a cancer,” and that shocks you. That is a big thing. It makes a big difference in a patient. “I have cancer now” is an important part that you have to acknowledge.

And then, you go to the next step, and now, let’s talk about treatment. Let’s talk about survival. Let’s not say, “I will not see my kids grow up.” These are not things – again, we cannot predict. We’re not gonna play God, and we can never predict if someone will respond or not, but we know from the data that we have so far that we have amazing remissions and long-term survivors. I have many of my patients that I transplanted 15 years ago still alive, doing well. Again, I cannot say that myeloma is cured, but we have a good remission rate currently.

Patricia:                      

Dr. Ghobrial, thank you so much for taking the time today.

Dr. Ghobrial:              

Absolutely. Thank you.

Patricia:                      

And, thanks to our partners. To learn more about myeloma and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Patricia Murphy.

An MPN Care Partner Shares Why He’s Optimistic About the Future

An MPN Care Partner Shares Why He’s Optimistic About the Future from Patient Empowerment Network on Vimeo.

Care partner Jeff Bushnell, husband of myelofibrosis (MF) patient advocate Summer Golden, explains why he’s hopeful about their future together. Jeff shares key resources that have helped him stay educated and maintain optimism.

Summer Golden and Jeff Bushnell have been married for over 20 years. When Summer was diagnosed with myelofibrosis (MF), Jeff took on the role of care partner and advocate. Summer uses her years of theatre training and comedy to cope with her condition and help others, while maintaining positivity about the future.

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Transcript:

Jeff:

It’s important to educate yourself because the more you know the less fear can overcome you. And this particular disease – the research is happening so fast, and things are changing. In my estimation, they’ll find – right now, the only cure is a stem cell transplant. It’s normally not done for older people. That in itself is innately risky. I’m convinced, probably within the next five to seven years, there will be a cure for this disease that’s not a stem cell transplant.

The research is moving that quickly on it. And if you don’t follow the disease and the people that are working on it, the specialists, you’re gonna have a much greater chance of feeling powerless and getting overwhelmed by it. As Summer believes, attitude can have a huge, huge impact on how the course of your disease runs. And a doctor would tell you the same thing.

For me, it started with Patient Power. Patientpower.info, I believe is, what it is. They have a whole section for myeloproliferative neoplasms and myelofibrosis, and they’re short videos. And you get a chance to listen to the best doctors that are the head people in this, Dr. Mesa, Dr. V [Verstovsek], and Dr. Jamieson – all the people that are really the movers and shakers. They speak. And you also get a chance to hear other patient’s stories and how they’re dealing with it. And that will give you a much better idea of what you’re facing. And you can really understand things from there. And you can get your knowledge.

Fear comes from lack of knowledge. In my job as a pilot, I flew for 50 years. I very, very rarely was afraid because my knowledge was so great and was reinforced every year by continual training that I felt prepared to handle anything that might come across to me. Knowledge is really important. It will allay your fears dramatically.

When I started online and heard about people that had been journeying with this for 10 or 15 years, initially, I had thought – well, this is a year or two, and it’ll be the end. And then I realized, plenty of people have lived with this for a long, long time. And they had a journey, and they’re doing it successfully. And that gave me confidence.

The more people you can talk to about it, the more you can put your journey in perspective. And it’s really hard to put in perspective for this particular disease because it affects everybody vastly differently. Some cancers – the progression is very, very linear. Everybody kind of goes through the same thing. This one – it depends on the mutations you have in your blood and all kinds of things like that, and some people get really bad symptoms quickly.

Others, they don’t. But the more you know about how those things affect you, the more you know and can understand about what to expect. And the more people you talk to who have it, you can find out about their journeys. It helps put yours in perspective.

I’m optimistic because I really keep up to date on what’s going on. And I see the doctors that are in the forefront of this and the research that they’re putting in and the care they have for working on this disease and the knowledge they have, and I just am quite optimistic. And as I say, I’m following the medical developments extremely closely.

I went to the ASH Conference last year. And I’ve gone to another conference that our doctor spoke at. And I’m just kinda blown away by – I’m fascinated by the science.

My advice would be find out as much as you can about it and support each other in a way that works in your own marriage.

Summer and I approach life a little bit differently. And yet, one of the reasons we do so well together is we kinda have both ends of the spectrum covered. And I sensed that when I met her 20 years ago. And we brought something to the table that each of us needed. And if you can find that in your relationship with your significant other that has the disease, what you can bring to it, what they can bring to it, you can be a tremendous support for each other.

A Care Partner’s Journey: How Life Goes on After an MPN Diagnosis

A Care Partner’s Journey: How Life Goes on After an MPN Diagnosis from Patient Empowerment Network on Vimeo.

Care partner Jeff Bushnell shares how he and his wife, patient advocate Summer Golden, have dealt with her myelofibrosis (MF) diagnosis. Jeff explains how online support and finding an MPN specialist were essential steps in helping them continue to live life to the fullest.

Summer Golden and Jeff Bushnell have been married for over 20 years. When Summer was diagnosed with myelofibrosis (MF), Jeff took on the role of care partner and advocate. Summer uses her years of theatre training and comedy to cope with her condition and help others, while maintaining positivity about the future.

 

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Transcript:

Jeff:

The worst part was initially. We didn’t get a myelofibrosis diagnosis.

It took about a month because in order to definitively diagnose it they have to take a bone marrow sample and send it to a pathologist and so on and so forth. So, all that time, I’m worrying about the possibilities. It could be leukemia or this, that, or the other thing. My way of handling and dealing with scariness – I’m a retired pilot – is to find out things, knowledge.

I spent a huge amount of time on the internet. The LLS Society has papers about it, and I read those.

And the more I got into it – once we found out it was myelofibrosis, I’ve read almost all of the papers that the doctors write for each other to find about this. That doesn’t interest Summer in the slightest. It interests me greatly. So, when we have an appointment with the doctor – when I’m talking to the doctor, it’s like two doctors talking to each other.

When Summer’s talking to her, they talk on a different plane. It’s much more about mental approach to things and that kind of thing.

And for me, when I think back to the beginning of when we had this and where we are now two years later, we’re living the life that we lived before she was diagnosed to be real honest with you.

We do everything that we did before she was diagnosed the same way we did it before, and it was a trip that probably everybody who gets diagnosed or deals with a person that has the disease takes. When it first happened, it hit us like bricks coming out of the sky hitting us on the face. Literally, when we first went to the hospital and she got the word that there was a problem – as I say, we lived in two separate houses – I literally was afraid to call her phone figuring she might be not there. I was that scared. And then, after we met our doctor, which was extremely fortuitous – when we went to the emergency room, the person that was there, she said these look like leukemia things.

So, she called the oncologist. The oncologist on call is our current doctor, Dr. Tiffany Tanaka, and she’s a specialist in this disease. It was like it was meant to be. And Dr. Tanaka asked the guy to do some other tests and then said, “Send her home, but tell her I need to see her this week.” So, we’re thinking all these horrible things. And its New Year’s weekend, so the clinic is closed for about five days, you know? We’re worrying and worrying and worrying.

We finally saw Dr. Tanaka, and it was like a breath of fresh air. This wonderful doctor has the ability to just communicate with the patients. I’m interested in the disease, so she communicated on my level. Summer is not interested in all the medical jargon, so she was able to explain to Summer what was going on and just very, very reassuring, very reassuring.

And then, I went and started getting information. That’s my way of coping with things. The first place I went was – I went to Patient Power and found a lot of information there.

And then I found the online myelofibrosis support group at Facebook. And that was very, very useful. When I started reading about the fact that some people had this for many, many years – then I said this is not – nothing’s gonna happen in the next year or two. We can go back to living. And once we learned more about it and spent more time with our doctor and Summer was able to live her life once she got taking the medicine – she takes Jakafi.

That controlled the basic symptoms, and we haven’t looked back. We just started living our life the way we had been living it before.

How Does Genetic Testing Impact Your MPN Treatment Options?

How Does Genetic Testing Impact Your MPN Treatment Options? from Patient Empowerment Network on Vimeo.

How can genetic testing results impact your treatment and treatment response? Dr. Ruben Mesa provides an overview of common mutations associated with essential thrombocythemia (ET), polycythemia vera (PV) or myelofibrosis (MF) and how identification of these mutations are moving research forward.

Dr. Ruben Mesa is an international expert in the research and care of patients with myeloproliferative neoplasms (MPNs). He serves as director of UT Health San Antonio MD Anderson Cancer Center in San Antonio, Texas. More about this expert here.

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Transcript:

Dr. Ruben Mesa:

We are learning much more about the genetics of Myeloproliferative Neoplasm, as we truly are about the genetics of many diseases. First, when I speak of genetics, these are not the genes we think of of inherited genes that are passed from mother and father, to son or daughter. These are the genes in ourselves that potentially can change over the course of our lives, and those changes or mutations can be associated with diseases.

So, what we have learned is that the genetic changes that are associated with myeloproliferative neoplasms are important, both in terms of predicting how the diseases might behave, and also, potentially in terms of therapies. The genetic changes fall into two different groups.

There’s a first group of the most common mutations that we think are important in driving the disease. The most common is the mutation in a protein called JAK2. That’s a mutation in about half of the patients with ET, half with PV – or half with myelofibrosis, and the majority with polycythemia vera. There is mutations in calreticulin. That’s about in a third of patients with ET, and a third with MF. And then, there’s mutations in MPL, which are present in a handful of patients with ET and with MF.

But in addition to those three mutations that tend to be mutually exclusive; patients tend to only have one of those, and there’s a small group of patients that do not have any of those three. But there’s another group of mutations that we have learned about.

That we are able to obtain on panels of sometimes anywhere from 40 to 100 genes that may or may not be changed or mutated in diseases like MPNs and the implications of what those pattern of changes in those mutations have for those patients. 

AML Genetic Testing: Could It Lead to a Targeted Treatment for You?

AML Genetic Testing: Could It Lead to a Targeted Treatment for You? from Patient Empowerment Network on Vimeo

AML expert, Dr. Pinkal Desai, outlines the reasoning behind the necessity of cytogenetics and molecular testing when managing an AML diagnosis. Want to Learn More? Download Your AML Navigator Resource Guide, here.

Dr. Pinkal Desai is an Assistant Professor of Medicine at Weill Cornell Medical College and Assistant Attending Physician at the New York-Presbyterian Hospital. More about this expert here.

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Transcript:

Dr. Pinkal Desai:         

So for patients who are undergoing molecular testing or any diagnosis of AML, both cytogenetics and molecular profiling are important, so they do not supersede each other. This is the conglomerate information that we need from the diagnosis to make important medical decisions. Usually the diagnosis would include: looking at the cells under the microscope by the pathologist; flow cytometry, which is a way to identify the subtype of leukemia; chromosomes or karyotypic analysis, which is to look at the individual chromosomes and whether they are abnormal in these leukemia cells; and the last one would be the molecular mutations, which would be single-gene profiling of the leukemia cells.

All of these are important, and it’s not that one can be omitted. They’re all part and parcel of the diagnosis of AML, and all of them should be done.  

So my advice to patients whenever this topic comes up of molecular mutations is always an unequivocal – there should be no question that this should not be done. The advice is plain and simple. This has to be done at diagnosis and, in certain cases, at relapse as well in order to figure out the best treatment possible. If they’re at a site or a clinic where this molecular testing is not available, then they should seek a second opinion to a site that would do this testing because in this day and age of leukemia, there is no treatment and diagnosis that can be done without all of these components in place.

In the old days, we didn’t have a lot of treatment in AML. It was either chemotherapy or hypomethylating agents, and that’s it. But now we have several drugs, five or six of them, that were just approved in the past two years specifically for leukemia and targeting some of these mutations. We have Midostaurin, Gilteritinib, Ivosidenib, Enasidenib, and I don’t want to go on and on about these drugs, but the most important thing is that in this day and age where you have so many drugs, how to incorporate these drugs into the management for patients, both upfront and in the relapse setting, it’s extremely relevant to do this testing, and this is highly encouraged and should be done as part of the diagnosis and treatment.

Fact or Fiction? AML Causes & Symptoms


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

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

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Transcript:

Ross:

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

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

 

Dr. Pollyea:

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

 

Ross:

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

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

 

Dr. Pollyea:

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

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

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

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

 

Ross:

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

 

Dr. Pollyea:

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

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

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

 

Ross:

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

 

Dr. Pollyea:

Yeah.

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

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

So, that’s the challenging balance.

 

Ross:

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

 

Dr. Pollyea:

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

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

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

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

 

Ross:

Is formaldehyde exposure another risk factor for AML?

 

Dr. Pollyea:

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

 

Ross:

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

 

Dr. Pollyea:

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

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

 

Ross:

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

 

Dr. Pollyea:

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

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

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

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

 

Ross:

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

 

Dr. Pollyea:

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

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

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

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

 

Dr. Pollyea:

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

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

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

 

Ross:                          

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

 

Dr. Pollyea:

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

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

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

 

Ross:

How easy is it to diagnose AML?

 

Dr. Pollyea:

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

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

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

 

Ross:

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

 

Dr. Pollyea:

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

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

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

 

Ross:

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

 

Dr. Pollyea:

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

 

Ross:

How important is early diagnosis?

 

Dr. Pollyea:

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

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

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

 

Ross:

What are the best ways to manage those symptoms?

 

Dr. Pollyea:

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

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

 

Ross:

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

 

Dr. Pollyea:

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

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

 

Ross:

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

 

Dr. Pollyea:

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

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

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

 

Ross:

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

 

Dr. Pollyea:

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

 

Ross:

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

 

Dr. Pollyea:

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

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

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

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

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

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

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

 

Ross:

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

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

 

Dr. Pollyea:

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

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

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

 

Ross:

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

 

Dr. Pollyea:

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

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

 

Ross:

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

 

Dr. Pollyea:

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

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

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

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

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

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

 

Ross:

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

 

Dr. Pollyea:

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

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

 

Ross:

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

 

Dr. Pollyea:

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

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

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

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

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

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

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

 

Ross:

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

 

Dr. Pollyea:

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

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

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

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

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

 

Ross:

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

 

Dr. Pollyea:

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

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

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

 

Ross:

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

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

Tag Archive for: cytogenetics

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