Tag Archive for: maintenance therapy

How Does Essential Testing Affect Myeloma Care and Treatment?

How Does Essential Testing Affect Myeloma Care and Treatment? from Patient Empowerment Network on Vimeo.

 Why is it important to ask about essential testing for your myeloma? Find out how test results could reveal more about your myeloma and may help determine the most effective care for your individual disease.

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Transcript:

Why should you ask your doctor about essential myeloma testing?

When a patient is diagnosed with myeloma, they typically undergo a series of tests that aid in diagnosing and staging their individual disease. The standard tests include:

  • Blood Test
  • Urine Test
  • Bone Marrow Biopsy, and
  • Imaging

As research in the field evolves, genetic profiling via more in-depth cytogenetic testing is increasingly common to further classify your myeloma. This testing often identifies unique biomarkers of the myeloma, such as translocations or changes in chromosomes.

So why do the results of these tests matter?

  • The presence of certain biomarkers can indicate a patient is low-risk, which can suggest a more positive prognosis.
  • There are certain biomarkers that indicate high-risk myeloma, meaning an aggressive treatment approach may be more effective.

Knowing your risk in myeloma is useful to your healthcare team when choosing a treatment approach or may help in determining if a clinical trial might be right for you.

How can you Insist on the best care for YOUR myeloma?

  • First, always speak up and ask questions. Remember, you have a voice in YOUR myeloma care. Your doctor is expecting you to ask questions and should be able to answer them.
  • Ask your doctor if you have had or will receive genetic testing for risk stratification and how the results may impact your care and treatment plan. Be sure to ask for paper or electronic copies of your important test results.
  • And finally, bring a friend or a loved one to your appointments to help you process information and to take notes.

To learn more about your myeloma and access tools for self-advocacy, visit powerfulpatients.org/myeloma 

Which Myeloma Treatment Is Right for You? What You Need to Know

Which Myeloma Treatment Is Right for You? What You Need to Know from Patient Empowerment Network on Vimeo.

What should you know before deciding which treatment is best for YOUR myeloma? Myeloma expert Dr. Saad Usmani reviews essential testing that may help guide treatment decisions, and discusses the impact of risk stratification on myeloma care. Dr. Usmani also provides an overview of treatments in development, the importance of clinical trials, and shares why he’s hopeful about the future of myeloma research.

Dr. Saad Usmani is the Chief of Myeloma Service at Memorial Sloan Kettering Cancer Center in New York City. Learn more about Dr. Usmani, here.

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Transcript:

Katherine:

Hello. And welcome. I’m Katherine Banwell, your host for today’s program. Today, we’re going to discuss how to access the most personalized care for your myeloma and why you should insist on essential testing. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Okay. Let’s met our guest today. Joining me is Dr. Saad Usmani. Dr. Usmani, would you introduce yourself please?

Dr. Usmani:

Certainly. Thank you for inviting me, Katherine. I’m Saad Usmani. I’m the incoming chief of myeloma at the Memorial Sloan Kettering Cancer Center in New York.

Katherine:

Excellent. Thank you for taking the time out of your schedule to join us today. Before we delve into the discussion, let’s start by defining a term that we’re hearing more frequently. What is personalized medicine?

Dr. Usmani:

Personalized medicine is a fancy term to examine different aspects of a patient’s health outside of their cancer diagnosis. And also, the cancer itself – factors that are associated with good response to treatment or an early relapse from treatment. So, it’s a holistic kind of an approach that looks at all of these factors together. Also, looks at the patient’s mental and social well-being and comes up with a game plan for them.

So, I would probably divide the various factors that kind of come into play with the personalized medicine or personalized approach to cancer treatment by taking into account factors that are patient-related, factors that are cancer- or disease-related, and then factors that are related to treatments that they maybe receiving.

So, these three kinds of combined together to form a plan that is unique to that individual patient.

Katherine:

Right. What tests are necessary to help understand a patient’s specific disease both at diagnosis and prior to treatment?

Dr. Usmani:

So, the testing includes – what’s the objective of testing – we do tests to help in diagnosis to assess how much of cancer we’re dealing with and then what kind of cancer we’re dealing with. Even within a given cancer, how much cancer you have and what kind you have is important. Folks can have a little bit of cancer in

terms of burden. But it can be aggressive in its nature. So, you can have King Kong at your door, or it could be the green giant just trying to serve up veggies. Whereas King Kong will bite your head off.

So, with that in mind, there are things that we do such as blood tests to see effects on blood counts, kidneys, liver. We also do certain blood tests to identify what kind of multiple myeloma a patient may have as an example. So, the kind of myeloma protein they’re secreting. The kind of light chain they’re secreting. Then urine tests are done to see if there are any proteins that are leaking through the kidneys if there is kidney damage. Then bone marrow biopsy to a) look at how much myeloma and b) what kind by specific testing that we do on the bone marrow biopsy. And then imaging to see what parts of the bone’s affected.

Katherine:

Great. I’m assuming that these tests will help with the opening of the stages of myeloma.

So, how is myeloma staged?

Dr. Usmani:

So, the staging of myeloma is still a work in progress. The reason why I say that is we have a good way of accessing how much myeloma a patient may have. But if we don’t combine it well with what kind or how aggressive it may be. So, staging in myeloma relies on two blood tests that are serum albumin and serum beta-2 macroglobulin.

And they help us give a good assessment of how much myeloma patients have. And maybe a little bit of information about whether patients may have a bit more aggressive kind. But then you overlay that with cytogenetic information from the myeloma cells that are from the biopsy as well as another blood test called LDH.

If patients have any of the quote unquote high risk features, they are – along with a high level of beta 2 microglobulin, you stage them as stage three. If they don’t have them, they’re stage one. If they have some of the features, they’re kind of in between in stage two. And that’s how we stage multiple myeloma.

Katherine:

You mentioned cytogenetics. What testing is involved in that?

Dr. Usmani:

So, bone marrow biopsy – it’s very broad. But there are two parts to it.

One part is getting the bone marrow aspirated where we insert a needle into the pelvic bone and get parts of the bone marrow – the blood inside the bones out. And look at how much percentage of plasma cells are there. What kind of surface markers or features they have.

And then we look at if those cancer cells have any chromosome abnormalities that are unique to myeloma. And some chromosome abnormalities can be high-risk.

What does high-risk mean? High-risk means if you treat patients in a certain fashion, they have a higher chance of relapsing or a higher chance of the myeloma coming back out of remission. So, we identify those features by way of looking at cytogenetics. And there are different techniques in which we can take a look at that.

Katherine:

And what are those techniques? There’s something called FISH, right?

Dr. Usmani:

Yes.

Katherine:

And flow cytometry and also next generation sequencing?

Dr. Usmani:

Yes. So, and there is also conventional cytogenetics. So, flow cytometry looks at the different proteins that are part of the surface of any cell – any blood cell for that matter. It could also be any other cell as well, not just blood cells.

But in this particular case when we do flow on the blood marrow aspirate, we’re looking for unique features of those myeloma cells. But that does not tell us anything about the chromosomes. Conventional cytogenetics is the old fashion way. It’s a 40 – 50-year-old technique in which you make the cells in a test tube. You make those cells go through cell division. Each human cell has 46 chromosomes or 23 pairs. And when the cells are dividing, those chromosomes kind of line up in the center.

And the old fashion technique of conventional cytogenetics was take a look at the cells when those cells – when the chromosomes are aligned, and see if some parts of the chromosomes are missing or one chunk of one chromosome has attached to the other. That’s the old fashion way. The FISH technique, what it does is it’s geared toward identifying specific abnormalities.

And one part of that particular protein or molecule that goes and attaches to that chromosome has a color-coded probe. So, you can see within a cell different colors light up. And based on those unique features, you can identify “Okay. This cell over here is missing a part of chromosome 17. Or this part of chromosome 14 is attached to chromosome 4.” That’s FISH. So, FISH is very specific. Conventional cytogenetics is not. Next-generation sequencing, there are – that’s a broad term. You can measure different types of nucleic acids: RNA versus DNA. And those different techniques identify specific – they can identify specific mutations in a cancer cell.

So, each of these techniques provide different layers of information for our myeloma patients.

Katherine:

Thank you for that explanation. I appreciate it. How can the results of these tests affect prognosis and treatment?

Dr. Usmani:

So, currently for the most part, we’re treating myeloma patients in a similar fashion. Except for some tweaking based on these quote unquote high-risk features. So, there are certain chromosomes abnormalities that tell us that a patient has a higher chance of relapsing early even if they get the standard of care treatment. So, we try to enroll those patients into a clinical trial or have better optimization of their induction treatment and their maintenance strategy.

So, identifying these high-risk abnormalities is important because our treatment decisions may be modified for that patient’s disease. Or we might be able to get them to a clinical trial sooner than later.

Katherine:

Right. What is risk stratification? And how is it used in patient care?

Dr. Usmani:

So, risk stratification helps us identify people who are going to do well in terms of getting to a good response and maintaining that response and maintaining being progression free or being disease free versus those folks who maybe relapsing sooner. And that’s called risk stratification. So, you are essentially identifying and dividing patients into two different buckets saying, “All right. I have to pay attention to this person a bit more because they can relapse soon. So, I’m going to be keeping an eye on their labs and such very much, much closely.”

Katherine:

Let’s talk about therapy for myeloma patients. How are low-risk patients treated?

Dr. Usmani:

So, typically, the low or standard risk patients are treated with at least a three-drug induction treatment at the time of diagnosis. Or sometimes with four-drugs if you combine an antibody treatment. There are various regimens but the standard of care is at least three drugs. Then for patients who may be eligible for a stem cell transplant, they go on to receive autologus stem cell transplant.

Once they’ve recovered from the stem cell transplant, they go on to maintenance treatment.

And the idea is that the induction along with stem cell transplant for those patients who are eligible gets patients to as deep as a response as possible. And the concept of maintenance is you maintain them in that response and delay the disease from coming back.

Katherine:

Right. And then what about high-risk patients? How are they treated?

Dr. Usmani:

So, for high-risk patients, we typically prefer using a four-drug regimen. Either daratumumab (Daralex) RVd or carfilzomib (Kyprolis) with len dex or KRd as induction treatment for high-risk patients. After the stem cell transplant, most patients would continue both the lenalidomide as maintenance along with the proteasome inhibitor. If f patients had low or standard risk disease, they would only be getting lenalidomide as maintenance. So, here for high-risk patients, you’re adding a proteasome inhibitor.

Katherine:

Right. I see. Okay. And where do clinical trials fit into treatment?

Dr. Usmani:

So, as a clinical researcher, I’m a big proponent of telling my patients that if there’s a clinical trial that’s available to you, it doesn’t matter which stage of disease you’re at. Whether you’re newly diagnosed, or another myeloma has come back. Consider a clinical trial as your first and best option. Talk to physicians about both the standard of care options as well as clinical trial options.

Most clinical trials in myeloma are not someone getting treatment and the other person not getting anything. The trials that we’re doing, patients are getting at the very least the standard of care treatment. So, I would say that the – yeah. I mean, the clinical trials end up being the best option for majority of patients instead of standard of care.

Katherine:

Who is stem cell transplant right for?

Dr. Usmani:

So, stem cell transplant are kind of a misnomer. There is nothing magical about getting your own – collecting your stem cells and giving them back to you. I think the stems cells are – the way that – what they’re really doing is helping the patients bone marrow recover from the melphalan chemotherapy that’s given as part of the stem cell transplant because it’s melphalan, which was our first anti-myeloma medicine discovered back in the ‘50s and early ‘60s. That has been a mainstay of treatment of myeloma for six, seven decades now.

But if you give high doses of melphalan, there’s certain side effects. It can damage the stem cells and delay blood count recovery. So, that’s why patients get stem cells. So, in the body of evidence we have, most myeloma patients would be eligible for a stem cell transplant either at the time of diagnosis or if they decide to collect their stem cells and hold it back for the first relapse. That would be the other setting. But age is not a barrier. It’s more about how fit a patient is. And this is where a comprehensive myeloma geriatric assessment becomes important because an eyeball test is not good enough. You need to have more complex assessment of patients. So –

Katherine:

So, this is looking at comorbidities.

Dr. Usmani:

It is looking at comorbidities.

It’s looking at performance status. It’s looking at cardiopulmonary reserve. It’s looking at cognition and mental health as well. So, all of those factors. And obviously besides that, if you don’t have good social support, then going through a stem cell transplant becomes a challenge as well. So, there’s all these factors that kind of come into play together.

Katherine:

Yeah. Dr. Usmani, how is immunotherapy advancing in this field?

Dr. Usmani:

I think that’s the big area of research and clinical therapeutics over the past five or six years is immunotherapies. And it’s a broad umbrella. There are a few things that kind of fall under it – under that category.

So, it includes antibody-based treatments, includes CAR T-cell therapies. Yeah. I mean, it’s a very active area. Again, we can have a one-day seminar just talking about all the advances that are happening in that specific space. But that’s the new frontier. I think that’s the immunotherapies play a big role in finding a cure for myeloma.

Katherine:

You mentioned CAR T-cell therapy. Is it showing a lot of promise in myeloma care and treatment?

Dr. Usmani:

It is in the relapse refractory as in the advance refractory patients as well as in early relapse patients. And we are just starting to do clinical trials in newly diagnosed, high-risk patients. So, yes. It’s showing good promise. One advantage of CAR T-cell therapy is once you get the CAR T-cell therapy, it’s a one and done deal.

You just get CAR T-cell therapy and there’s no maintenance. So, patients really enjoyed that part of being off of therapy. They go into remission and then they don’t have to take anything for months or even a few years. So, I think that’s the biggest excitement about CAR Ts.

Katherine:

Yeah. Once a patient begins therapy, how do you monitor whether a treatment is working?

Dr. Usmani:

So, as part of the diagnostic work up, we typically have identified in the blood using serum protein electrophoresis and serum free light chains. What kind of myeloma proteins these – that particular patient’s myeloma cells are making. And we can monitor them every cycle of treatment. So, every three or four weeks.

And that’s the most noninvasive way of seeing if the treatment is working. The second obviously important thing is if someone has symptoms. If they have kidney damage, if they have bone pain, all of those things start improving as you’re getting treatment. And then in some patients, we’re also looking at imaging like PET CT scans at certain time points. And at some point, we do also look at the bone marrow biopsies to see what’s really going on in the factory.

Katherine:

We often hear the term MRD, or minimal residual disease used in the myeloma space. So, what is it exactly and how is it used in patient care?

Dr. Usmani:

So, minimal residual disease is a way to measure how much myeloma is left over in a given patient.

And historically, we were simply looking at the serum proteins and the light chain levels along with just the morphology of the bone marrow to see if – kind of determine a response. But we can have a much deeper assessment of how many cancer cells as a leftover from a bone marrow biopsy by different measurements. Someone can be in a complete response with M-Spike is gone. The light chains have normalized.

Yet they can still have 10,000 – 100,000 myeloma cells still in the bone marrow. And just using the bone marrow biopsy the way that we used to, we won’t be able to see them. We’ll just see, “Oh, these look like normal plasma cells.” So, using next generation sequencing and flow cytometry, we can look at normal myeloma cells at a very deep level – one out of one million.

But these tests are highly specialized. And especially the flow cytometry requires a lot of expertise. The NGS requires good sampling at the time of diagnosis as well as subsequent specimen.

Katherine:

Here’s a question we received from a viewer before the program. Mary writes: “I was just diagnosed with MGUS, and I’m obviously very concerned. What should I be looking for and how often should I check in with my doctor?”

Dr. Usmani: That is a very good question. MGUS is a precursor disease to myeloma and other class cell muscle disorders. And based on the original homestead county data from the mayo clinic, if there were 100 folks who had MGUS, one out of 100 every year would – there’d be one percent likelihood of them progressing to myeloma or some other plasma cell disorder.

So, the overall risk say in the next 20 years for a given patient is fairly low. And what we look at when we’re determining how frequently to check the blood or see the patient is the value of that M-spike.

If it’s a high value, if it’s two or three, we’ll be checking the labs more frequently every three months or so. Maybe seeing them every six months for the first year or two. If the M-spike value is very low, it’s one gram or less, we might be just checking labs once or twice a year and seeing patients once a year. But I would highly recommend in addition to seeing your regular hematologist who diagnosed you with this MGUS to do seek an opinion at a myeloma center of excellence.

Katherine:

Okay. If a patient is interested in participating in a clinical trial, what question should they ask their doctor?

Dr. Usmani:

The question that they should ask each time when you’re at that fork is can you please share with me what clinical trial options I have and compare them. Give me more information about “How do they compare with the standard of care treatments that are being offered?” And if you do not have any clinical trial options, would it be worthwhile, to again seek an opinion at a myeloma center of excellence to see if there are clinical trials available.

And in today’s day and age, you can have a virtual consult with a myeloma center of excellence. You don’t have to even go in. You can just chat with an expert on video and see if a clinical trial maybe right for you.

Katherine:

Are there common misconceptions you hear from patients concerning clinical trials?

Dr. Usmani:

Yeah. I think the most common perception patients have is “Oh, I’m going to be used a Guinea pig for something that hasn’t been used in humans before.”

Katherine:

In a human before. Exactly.

Dr. Usmani:

So, most of the clinical trials are not first in human trials. Yes. We do have first in human trials where we are using novel treatments in some instances.

But there is strong rational and safety guardrails built around that. And if you’re participating in a first in human study, it’s highly likely that the other treatments have stopped working and there might not be other options. However, majority of trials that patients end up participating in are getting at least the standard of care treatment. So, I think it’s very clear to kind of communicate this to patients that, “Hey, you are going to be getting a standard of care treatment even if you go on the quote unquote control arm. It’s not that you’re getting placebo.”

So, I think clarifying what the protocol is, giving patients information kind of alleviates some of those concerns. But that’s the most common misconception people have.

Katherine:

If patients are concerned about voicing their concerns and I think many of us are, why should they feel like they’re a partner in their care?

Dr. Usmani:

Well, that’s the only way that they will feel empowered. And we have to remember why we’re doing this, right? So, we’re doing this so that we can alleviate the burden of this disease from our patients and give them as good of quality of life as possible. And it’s a partnership. And in that partnership, the patient is the most important partner. Everyone else – it’s like you’re the main character.

The patient’s the main character in the movie. And all of us are supporting cast around them. I think that’s how you have to approach it. That’s how – that’s why it’s very important. And of course, patients – we’re not expecting our patients to read the papers and be knowledgeable about everything. But have a general sense of what to expect and it will be – so, having a more educated patient helps them deal with treatments better and have realistic expectations of what’s to come.

Katherine:

Right. As I mentioned at the start of this program, Dr. Usmani, patients should insist on essential myeloma testing prior to choosing a treatment. As we conclude, I think it’s important to point out that some patients may not know if that can even receive these important tests. So, what key question should they ask their physician about them?

Dr. Usmani:

So, you should be asking your physician about what kind of myeloma you have? What stage of myeloma you have? How much involvement in the bones you have? Do you have any chromosome abnormalities or any features of disease that put you at a higher chance of the myeloma coming back?

As you ask these questions, your physician will be prompted to think about “Okay. Am I missing something in my work?” And you can always ask is there anything else you need to do in terms of testing to give you a better idea of how best to approach my treatment and follow up.

Katherine:

I’d like to close by asking about developments in myeloma research and treatment.

What’s new that you feel patients should know about?

Dr. Usmani:

Oh, my. We can spend a long time with this answer. I would say that we understand what’s driving myeloma as a disease. We have a better understanding of what’s going on with the rest of the immune system and the bone marrow microenvironment where the myeloma cells live. So, the treatments that are being developed right now are trying to combine different ways in which you can shut the myeloma cell down by targeting those abnormalities or those abnormal pathways. And also, to harness the patient’s immune system to go after the cancer cells. So, combining what we’re calling immunotherapy with small molecule or more cancer directed treatments.

So, I think that’s kind of where the field is headed. And it’s – these are smarter strategies, smarter treatments. And we’re moving away from old fashioned conventional chemotherapies.

Katherine:

Dr. Usmani, thank you so much for joining us today. It’s just been a pleasure.

Dr. Usmani:

It’s been my privilege. Thank you so much for inviting me to this.

Katherine:

Thank you. And thank you to all of our partners.

To learn more about myeloma and to access tools to help you become a more proactive patient, visit PowerfulPatients.org. I’m Katherine Banwell. Thanks for joining us today.

 

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What Should You Ask Your Doctor About Myeloma Testing?

What Should You Ask Your Doctor About Myeloma Testing? from Patient Empowerment Network on Vimeo.

Testing and test results may affect your myeloma care and treatment. Dr. Nina Shah, a myeloma expert, shares key questions to ask your doctor about testing and reviews testing techniques for myeloma. 

Dr. Nina Shah is Associate Professor of Medicine in the Fepartment of Medicine at the University of California San Francisco (UCSF) and treats patients at the Hematology and Blood and Marrow Transplant Clinic at UCSF Helen Diller Family Comprehensive Cancer Center. Learn more about Dr. Shah, here.

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Transcript:

Katherine Banwell:

If a patient wants testing beyond the standard, what should they be asking their doctors for?

Dr. Shah:

Well, thankfully a lot of these tests can be done as a standard. We actually have some approved testing for it. So, the most important thing is to ask the doctor at all. For example, the patient may ask, 1.) “When will my next bone marrow biopsy be?” and 2.) “When I get that bone marrow biopsy, will you be looking at cytogenetics and FISH?” and 3.) “When you get the bone marrow biopsy, will you be also looking for minimal residual disease?” And finally, “What technique will you use to look for that minimal residual disease?” There are different ones that the patients might find useful to know about.

Katherine Banwell:

What are some of the different techniques?

Dr. Shah:

There are a variety of ways that we can look for minimal residual disease. One of them is called flow cytometry. What that is is you send all the cells that are in the bone marrow through a chute, and in that chute you can sort of detect one or however many cells that are – that have a specific characteristic on their cell surface.

You think of it as a bunch of balls with lollipops sticking out of it. And based on the characteristics of those lollipops, you can tell if there are any plasma cells or myeloma cells. Another thing we do with minimal residual disease, another technique, is called the next-gen sequencing or NGS.

And for that, we need to know the specific DNA sequence that is very personal to your myeloma cells. So, your particular plasma cell or the cancer cell will have a sort of sequence, a specific sequence that can be identified when you’re first diagnosed. And if you have access to that tissue, that can be sent off to the company, and they use that as sort of a template or a measure – an individual identification. And then, they scan the subsequent bone marrow samples against that to see if there’s any sequence that matches that original one, and that’s the way you can detect one in a million positive cells, if there are any. 

How Is Minimal Residual Disease (MRD) Testing Used in Myeloma Care?

How Is Minimal Residual Disease (MRD) Testing Used in Myeloma Care? from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Nina Shah explains minimal residual disease (MRD) and how the results of this test may impact patient care and treatment.

Dr. Nina Shah is Associate Professor of Medicine in the Fepartment of Medicine at the University of California San Francisco (UCSF) and treats patients at the Hematology and Blood and Marrow Transplant Clinic at UCSF Helen Diller Family Comprehensive Cancer Center. Learn more about Dr. Shah, here.

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Transcript:

Katherine Banwell:

What is minimal residual disease testing, and when should it take place?

Dr. Shah:

Minimal residual disease is exactly what it sounds like. It’s the disease that you can’t see under the microscope, but it’s still there.

And I sort of equate it to the little deep food particles that are in a pot after you clean it and really, really scrub it, but still, something is in there. And that’s what it is for myeloma. And really, that depends on how sensitive your test is. We now know we can test for at least one in a million cells by some advanced techniques, and we like to test to see if there’s any disease left after certain treatments are done – for example, after a patient undergoes an autologous stem cell transplant.

Katherine Banwell:

What impact do results have on care decisions?

Dr. Shah:

Minimal residual disease testing can be useful for patients to understand the true burden of their disease. For example, it may be that there’s no more M-protein in the blood, or the light chains are normal, or even the bone marrow showed no plasma cells. But the minimal residual disease testing may show that, in fact, there are a few cells still in there, and that can help patients to decide, “Yes, I want proceed with maintenance therapy,” for example, or “No, I would not like to.” Although, we generally recommend it, patients like to have as much information as possible to make their decisions. 

How Are Cytogenetics Used in Myeloma Care?

How Are Cytogenetics Used in Myeloma Care? from Patient Empowerment Network on Vimeo.

Myeloma expert, Dr. Nina Shah, explains cytogenetics and how results of these tests affect care and treatment for myeloma patients.

Dr. Nina Shah is Associate Professor of Medicine in the Fepartment of Medicine at the University of California San Francisco (UCSF) and treats patients at the Hematology and Blood and Marrow Transplant Clinic at UCSF Helen Diller Family Comprehensive Cancer Center. Learn more about Dr. Shah, here.

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Transcript:

Katherine Banwell:

What is cytogenetics, and how is it used in myeloma patient care?

Dr. Shah:

We use the term cytogenetics and FISH sort of interchangeably, and really what it is, is the DNA characteristics of the bad plasma cells. So, the myeloma cells, and a lot of them may have changes in their DNA that are what we call clonal, meaning that they’re in a significant percentage of those cancer cells, or they might be non-clonal, which are less significant. But it’s the way the DNA is put together or maybe cut and pasted so that it changes the characteristics and maybe the aggressiveness of the disease.

Katherine Banwell:

What is the goal of this in-depth testing? Are there specific markers you’re looking for?

Dr. Shah:

When we look for things like cytogenetics and send FISH testing, we look to see if patients have changes that might make their disease may be more aggressive.

For example, it may cause their plasma cells, the myeloma cells, to grow faster or more aggressively. So, we look for changes that might, for example, have a deletion of a certain chain that puts the brakes on tumors, or it may have a translocation, which is when the chains sort of do-si-do together and that makes the cells grow faster. 

Understanding Your Role in Myeloma Treatment Decisions

Understanding Your Role in Myeloma Treatment Decisions from Patient Empowerment Network on Vimeo.

Many factors are considered when choosing a myeloma treatment. Dr. Nina Shah, a myeloma expert, reviews how treatment decisions are made and the patient’s role in deciding on an approach.

Dr. Nina Shah is Associate Professor of Medicine in the Department of Medicine at the University of California San Francisco (UCSF) and treats patients at the Hematology and Blood and Marrow Transplant Clinic at UCSF Helen Diller Family Comprehensive Cancer Center. Learn more about Dr. Shah, here.

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Transcript:

Katherine Banwell:

What are the main factors that you take into consideration before a treatment approach is decided on?

Dr. Shah:

We always have to remember that treating a patient is also treating a person. So, it’s not just about what the disease the patient has but who the patient is. And so, we take into consideration goals that the patient as well as other health factors that may take – be taken into consideration. For example, the patient may have high blood pressure or a heart condition. But regarding the disease, we really also take into consideration what the profile of the disease is, maybe how much disease burden the patient has and some genetic factors that may impact our decision-making.

Katherine Banwell:

What is the patient’s role in treatment decisions?

Dr. Shah:

The patient should always be the center of the decision-making. I think that’s a really important thing for us to remember because ultimately, it’s the patient who has to make the decision and has to withstand the treatment. Alongside of that there may be some caregivers as well, but the patient has to, 1.) understand the disease, and 2.) understand the treatment options. So, it’s best if the patient has as much information as possible.

Katherine Banwell:

Are treatment considerations different for patients with relapsed disease?

Dr. Shah:

For patients with relapsed disease, there’s a lot of things to consider that may not have been true when the patient was first diagnosed. For example, you always have to think of what maybe the patient had as a prior – excuse me, as a prior treatment, and also how the patient tolerated it. 

What You Should Know About Myeloma Clinical Trial Participation

What You Should Know About Myeloma Clinical Trial Participation from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Nina Shah shares her view on why patients should consider a myeloma clinical trial and provides advice for finding and participating in a trial.

Dr. Nina Shah is Associate Professor of Medicine in the Department of Medicine at the University of California San Francisco (UCSF) and treats patients at the Hematology and Blood and Marrow Transplant Clinic at UCSF Helen Diller Family Comprehensive Cancer Center. Learn more about Dr. Shah, here.

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Transcript:

Katherine Banwell:

Why should a patient consider participating in a clinical trial?

Dr. Shah:

I am a huge fan of clinical trials, as you probably figured out. And the reason for that is that it’s the only way we know how to do things. And for everything we figured out about myeloma, it’s because patients participated beforehand in clinical trials. So, of course, it’s a way to pay it forward. But aside from that, there’s an experience that a patient can have on a clinical trial that is really unlike other experiences that patients may have. For example, they will be given the opportunity to understand a lot about their disease that maybe they may not have understood before, and they may have the opportunity to try a treatment that might be beneficial.

There are no guarantees in a clinical trial, and that informed consent procedure where the doctor tells you about the risks, benefits, and alternatives, should be very comprehensive and clear. But it does allow for patients to get access to something they may not have had before. And I think one of the other things that’s important is that it’s sort of a concierge service, I would say, with clinical trials, because you have to be monitored very closely. So, of course, all your symptoms have to be known. And you get a little bit more time, I would say, when you participate in a clinical trial because we really want to know the pluses and minuses of these treatments.

Katherine Banwell:

How can patients participate in research? Where do they start?

Dr. Shah:

Participating in research is a great opportunity for patients and something that we’re grateful for as myeloma physicians. There are many ways to look on various websites. There are things like SparkCures. There’s ClinicalTrials.gov. You can look at any academic website. Almost all advocacy groups also have opportunities for you to look at clinical trials.

And any time you get the opportunity to look at patient education sites, they may have a link for you to look for other clinical trials that might be relevant to your particular stage in disease or the particular kind of myeloma that you have. When in doubt, please, if you have a chance, talk to your local oncologist perhaps to maybe refer you to a myeloma specialist. We can do this by Zoom now, so there should be no reason that we can’t be a part of your care team at least for a consultation. 

An Expert’s Hopeful Outlook on Myeloma Research and Treatment

An Expert’s Hopeful Outlook on Myeloma Research and Treatment from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Nina Shah shares why she’s hopeful about research and treatment, including immunotherapy and CAR T-cell therapy.

Dr. Nina Shah is Associate Professor of Medicine in the Department of Medicine at the University of California San Francisco (UCSF) and treats patients at the Hematology and Blood and Marrow Transplant Clinic at UCSF Helen Diller Family Comprehensive Cancer Center. Learn more about Dr. Shah, here.

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Transcript:

Katherine Banwell:

Is there emerging myeloma research that you feel patients should know about? And what are you excited about?

Dr. Shah:

There are so many aspects of myeloma treatment and the patient’s journey that we have been looking at. One of the things that I’m most excited about and I do a lot of research in is immunotherapy, which includes both CAR T-cell therapy as well as natural killer cell therapy and bispecific T-cell engager and other novel immunotherapies.

And I think these are interesting, because they allow for the patient’s own immune system sometimes to be used to kill the myeloma. And that’s something that is spring-boarding the way we treat myeloma to give patients better outcomes with less toxicity, if you can believe that. So, we’re really excited about that.

The other thing I’m really excited about is patient experience research that we’re doing. We now know that multiple myeloma patients live for maybe over a decade, and those patients are on a marathon of treatment; and how that treatment is a part of their life is very important in their experience as a patient. So, we’re trying to make that easier for patients as they go through, for example, transplants or maybe immunotherapy to give them more information, more control and more ability to talk about their symptoms with their provider and their care team.

How Does Myeloma Testing Affect Care and Treatment?

How Does Myeloma Testing Affect Care and Treatment? from Patient Empowerment Network on Vimeo.

What is cytogenetic testing in myeloma? Donna Catamero, a nurse practitioner specializing in myeloma, describes this in-depth testing, including the FISH test, and how the results impact the care of patients.

Donna Catamero is Associate Director of Myeloma Translational Research at Icahn School of Medicine at Mount Sinai Hospital in New York City.

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Transcript:

Katherine:

Blood and urine tests, bone marrow biopsy and imaging tests are all standard following a myeloma diagnosis, but what about more in-depth testing?

Because the terminology around biomarker testing varies, can you help break this down for patients, and how this in-depth testing is referred to in myeloma?

Donna:

So, biomarkers is a term that is commonly tossed around in many different cancer diagnoses and it means different things. But in general, it’s characteristics that can inform us about a diagnosis, about a patient’s prognosis and about their response to treatment. So, this can include things that we measure in the bloodwork, in the urine, even imaging. These are all things or markers that we look at to determine a patient’s either, like I said, response or risk stratification.

Katherine:

What about cytogenetics? What is that exactly and does that fit under the umbrella of biomarker testing?

Donna:

Yeah, so cytogenetics is a genetic snapshot of a patient’s cancer. So, it will give us a sense of how the disease will – the characteristics of how it will behave. But again, it’s just a snapshot and it’s not a precise science but certain mutations or certain genes will kind of inform us like “This might be maybe a more aggressive form and we need to do X, Y and Z.”

Katherine:

Which of these more in-depth tests are necessary in myeloma? Let’s start with the FISH test.

Donna:

So, FISH is a cytogenetic technique. So, what we do is, when we do the bone marrow, we send that off and we look at the genetics. Like I said, it’s a snapshot. And certain mutations will put patients in different risk stratifications, so we normally do this at the time of diagnosis and then with each relapse.

Katherine:

It seems that all of the test results can aid in determining outpatient’s risk. So, why is risk stratification so important?

Donna:

So, risk stratification is important.

It will give us a sense of how a patient might respond to certain treatments. Maybe a patient won’t respond as well to a stem cell transplant as someone with standard risk. So, we take this into account, but in this current time, in 2021, we don’t typically change our treatments according to risk. That’s why clinical research is very important because we’re studying right now patients with high-risk cytogenetics, do they do they better on certain therapies.

Katherine:

How do the results of these tests affect treatment choice and prognosis?

Donna:

So, someone who might have high-risk cytogenetics, we might want to be maybe more aggressive with our therapy. So, we might change how we want to maintain a patient. Usually, after a stem cell transplant, we give patients maintenance therapies. So, patients who have high-risk disease, we might change our strategy and have a more aggressive regimen in that maintenance setting. And with patients with higher risk, we probably will monitor them very, very closely in case – looking for signs for relapse. 

How to Play an Active Role in Your Myeloma Treatment and Care Decisions

How to Play an Active Role in Your Myeloma Treatment and Care Decisions from Patient Empowerment Network on Vimeo.

How can you actively participate in your myeloma care and treatment decisions? Engaging with your healthcare team is essential and may lead to better overall outcomes. In this program, Dr. Rafael Fonseca provides tips for how best to advocate for yourself or a loved one, as well as tools for making treatment and care decisions.

Dr. Rafael Fonseca is the interim director of Mayo Clinic Cancer Center and serves as the director for Innovation and Transformational Relationships at Mayo Clinic in Arizona. Learn more about Dr. Fonseca here.

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Transcript:

Katherine Banwell:    

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to explore how to engage with your healthcare team when diagnosed with myeloma, and we’ll discuss the patient’s role in care decisions. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Let’s meet our guest today. Joining me is Dr. Rafael Fonseca. Dr. Fonseca, welcome, and would you please introduce yourself?

Dr. Rafael Fonseca:   

Yes, of course. Happy to do that. Thank you very much, Katherine.  

I am a hematologist/oncologist, but I specialize in the area of multiple myeloma. I work at the Mayo Clinic in Arizona. I currently serve also as interim executive director for the Mayo Clinic Cancer Center that is at large across the Mayo Clinic enterprise. But at heart, I’m a myeloma doctor and I love to take care of myeloma patients. I devote my research and the rest of my academic activities to the field of myeloma.

Katherine:                  

Excellent. Thank you so much for joining us today. Let’s start with a question that’s on the mind of many of our audience members. We’re hearing that the COVID-19 vaccine is safe, but how effective is it for myeloma patients?

Dr. Fonseca:               

Thank you. I think that’s a fundamental question. It’s hard to know precisely how to gauge effectiveness when it comes to vaccination because historically, we know that is done by measuring antibodies and there’s a number of publications that are addressing this.

The concern has been two-fold. One is that because the disease itself is something that starts from the person’s immune cells become cancerous, that perhaps that would prevent them from having a very good response. Number two, and perhaps more importantly, will the treatments that are used for myeloma, etc. or lymphoma, can they interfere with our ability to mount an effective immune response? I think the response is mixed right now. I think I tell all my patients the upside is much better than the downside. I think we have a good record now of the safety of this product. I encourage everyone to get their vaccination.

I think it’s important to discuss this with your healthcare provider because sometimes people say, “Should I stop a little bit so that I can get a better response?” While it’s theoretically possible, we don’t want people to stop treatment if they don’t have to do that. Just my very last quick comment, the good news is that the community transmission is clearly going down as more and more people have participated in the vaccination.

We have more people who now have participated in this level of immunity that we have in the community. Hopefully, for patients as well as for their families, the risk of contracting this will continue to decrease.

Katherine:                  

Yeah. We can only hope. Well, let’s learn a little bit more about the disease itself. Dr. Fonseca, to level set with our audience, can you help us understand myeloma?

Dr. Fonseca:               

I’m happy to do so. Multiple myeloma is a cancer form of the bone marrow that arises when the cells that under normal circumstances protect us by the formation of antibodies. These are called the plasma cells. They become malignant. Myeloma is the last stage of a process where a plasma cell can go through a benign tumor or benign phase, if you may, something we call the monoclonal gammopathy, which by the way is quite common. About two percent of people over the age of 50 have this abnormality. Think of it like the colon polyp, a precursor condition.

There’s an intermediate stage that we call smoldering multiple myeloma, which is just more growth, but not quite at the level that it creates problems for the individual.

Then lastly, what we just simply call multiple myeloma, and that is when the growth of those cells becomes of such magnitude that a person starts having problems or starts having symptoms related to that. These cells live predominantly inside the bones in the space we call the bone marrow. They can do a number of things that actually lead to the symptoms and to the clinical presentation. As they grow in the bone marrow, they take some of that real estate.

A person may experience fatigue and that is because they have anemia.

The myeloma cells are also very characteristic because they can erode into the structure of bones, so destruction of bone is another feature that we see in patients with myeloma. That can be either seen on x-rays or sometimes people will present with symptoms related to bone pain or discomfort with movement or weight bearing. Those are signs that we look for.

Lastly, the myeloma cells product proteins and some of the fragments of those proteins can be damaging to the kidneys. Occasionally, people will present with decreased kidney function and sometimes outright failure of the kidneys. Those are the common presentations. It is a disease that mostly affects people in their 70s. It is not something that you can detect through routine testing; it’s just indirectly we start seeing abnormalities and then we do the right testing. If anyone is hearing this, of course, they need to have a detailed discussion with their own provider.

Katherine:                  

Of course, yeah. When a person is diagnosed with myeloma, they usually have a whole healthcare team. Who is typically on that team?

Dr. Fonseca:               

Absolutely. Let me start by saying the key to the successful management of myeloma is to have a well-organized team. It’s a disease that requires an integrated approach that usually brings around the patient a physician.

As part of my team, we also have advanced practice providers. We work with nurse practitioners that help us do the longitudinal care of patients. We have the nursing team. Every time I meet a new patient, I make it a point to bring my nursing team into the room so they can put a name and a face together, as patients will be interacting, of course, with a nursing team through the portal and the various visits. We have a team that is in charge of the chemotherapy administration. That is usually a separate a nursing team that is in charge of the administration of the medications. But we really don’t stop there.

We have pharmacists who help us review the medications for our patients. Very importantly, we have social workers that help us address psychosocial needs, as well as some of the practicalities that become inevitable when one deals with a serious diagnosis like multiple myeloma.

Katherine:                  

Yeah. Lately, we’ve been hearing this term, “shared decision making,” which basically means that patients and clinicians collaborate to make healthcare decisions, and it can help patients to take a more active role in their care.

I’d like to get your thoughts, Dr. Fonseca, on how best to make this process work.

Dr. Fonseca:               

We are very fortunate to live in this time of medicine, where ultimately, we recognize that the patient is the person expert. It is the patient decisions that should drive what is to be done in a situation. Whenever I interact with patients, I tell them, “Listen, I’m going to be like your counselor. I will provide you with options of what I think is reasonable. I will go to different degrees of effort in trying to convince you one way or another for a particular intervention. But at the end of the day, I only do a good job if I present you with the options and the pros and cons of those various approaches.”

I weave that into my language on every single conversation we have with patients. I think we’re way past the time where a physician would come and say, “This is what you’re going to do,” or “This is what will happen.” My language always includes, “I would recommend this.”

“I think the next best step for you to consider would be X, Y, or Z.” But ultimately, I look at patients and not infrequently at the person next to them, a family member or a close friend, and I say, “You’re the boss and with the person next to you providing additional support, comment, and guidance, we can together reach the best decision of what should proceed.” I think we’re incredibly fortunate because patients have access to sophisticated information, especially patients that have serious conditions such as would be cancer and, in my case, myeloma.

As an example, when I work with general internal medicine residents that work with me learning about hematology, I sometimes tell them, “You’re gonna walk into a room. Are you gonna be seeing what I say, this is like a tennis match between professionals. Are you gonna see the level of questions that patients are going to be asking me? They’re going to be asking me about the latest study that was presented at this meeting and the P value and this and that.”

“I can guarantee you that you would not have the tools to be able to address all those questions, simply because there’s such an in-depth understanding of the disease.” I realize this is not everyone. I’m giving you an extreme example. There are individuals that need additional support, more resources. But just to interact with someone who has such commitment to understand their disease and to help us by that understanding make the right decision makes my job so much more rewarding.

Katherine:                  

What do you think is the role of a patient then in their care?

Dr. Fonseca:               

I think it needs to be … I’m describing in some detail and there’s a lot to unpack there. Of course, patients are dealing with a very serious diagnosis. It’s okay to have periods where they are in a pause moment and they’re reflecting of what their facing, and that they can gather information from close family members.

I think we, as providers and the medical team, need to deliver a message that provides clear options for them as far as what the best next phase of their treatment or their management might be, including observations or supportive care. But the patient ultimately is a person who has to make that decision. I frequently get the question, and this is not surprising, and it happens all the time. A patient tells me, “What would you do if this was a family member?” I always tell them, “I always talk to you as if you were my family member, as if you were my brother, my mother, my father.

So, I try to live deeply to that fiduciary responsibility I have to your well-being. I recognize that there are circumstances, and that’s part of the finesse and the art of medicine, that I have to help a little bit more walk you through that step. Sometimes, it’s just human that one may want to say, I just want to disconnect. Maybe I’m not the person that wants to go and read in detail. But perhaps I have my daughter or my son who are helping me and understand better where things are.”

I think one of the key aspects of my role is to make sure that I have a sense that the person has a good understanding to be able to make an informed decision. At the end of it all, if the person decides to proceed in such way that doesn’t necessarily align with what I’m trying to do, I’m deeply respectful of that choice. I will go to extra lengths. So, if someone is foregoing treatment, when I know their treatment has a high likelihood of improving their quality of life, relieve a symptom, or improve survival, I don’t think I would do a good job if I don’t present why that’s so important. But ultimately, it is the patient’s decision.

Katherine:                  

Related to what you’ve just been speaking about, we have a question from the audience. This one is from Sarah. Her question is, “What advice do you have for caregivers? How can I be supportive during appointments?”

Dr. Fonseca:               

That’s a great question.

I have experienced this both as a physician, as well as a caregiver myself to someone who has had a cancer. I think I’m gonna say that there are several roles that caregivers play. Some of them are obvious and I’m gonna call them practical or perhaps even pedestrian, you know, organizing the activities of every day. That’s important, but a lot of people can do that. The second role is to be in assistance for the knowledge that is needed for some of this decision making. Sometimes patients can be overwhelmed, and we need some support and some vetting and peer process from a trusted and loved person so you can go through that.

That is very helpful, but what is essential, and the number one thing is you are first and foremost the loving family member or friend of that individual who is living through a very profound human experience. I think the first role of a caregiver has to be to express that role.

I, myself, reflect on moments where perhaps in a quick, reactive way I wanted to solve some of the immediate practicalities and what was needed most was a direct support. Even if I face a situation today, if I was, again, a caregiver for someone with a serious diagnosis with cancer, I would start with that priority. Number one, you are the support and the loving person. Number two is I will try to provide information. And number three, hopefully you can help with meals and the driving and what have you. But there’s many more people who can come and help in that regard. Not a lot can do the first part.

Katherine:                  

Right, absolutely. Yeah, those are excellent points. Let’s talk about treatment goals. What are the goals of myeloma treatment from a clinical perspective?

Dr. Fonseca:               

I’ve been very fortunate, also, to live through this era when we have seen a plethora of studies and new drugs being approved for the treatment of myeloma.

When I first started, I used to say no one wanted to do myeloma because we didn’t have good treatments. People wanted to study leukemia, lymphoma. It just turns out that this is probably one of the most vibrant areas of hematology from a science and from a clinical research perspective, of course. If I see young patients who have multiple myeloma, I have essentially two goals. The first one is to induce the deepest possible response I can do so in a safe manner. I also repeat, “in a safe manner.” But I really have the goal to try to induce the deepest response possible because that has translated and continues to translate, and in many ways proven to be associated with an improvement on their longevity and the time we can control the disease.

And it leads me to second goal, and that is that I firmly believe there is a subset of myeloma patients that are cured from their disease.

Now, this is possible because of the availability of these new treatments. I will only be able to say that in 10 and 15 years from now, when we have monitored patients for a long period of time, and we have been able to see that became true. But by all indicators, we have patients that are living many, many years without the disease coming back. I think that would be important. Now, we have patients that with more advanced age sometimes it’s difficult to propose some of the most intense form of treatments like stem-cell transplants.

We don’t do a lot of that in individuals over the age of 72 just because the toll that it takes on a person is very high, and the risks become higher. But still, in that population, providing the best treatment possible becomes a goal because I think more and more, we’re seeing patients in that age category that can start to get close to what normal life expectancy would be. It’s not there. It’s not perfect, but you start to get close. Lastly, if someone asked me, I have that balance between quantity and quality, the good news in myeloma, if you do it right, quantity and quality go hand in hand.

So, effective treatment provides symptom relief and provides durability of responses.

Katherine:                  

That’s excellent. What other factors do you consider when determining a treatment approach?

Dr. Fonseca:               

The human experience that comes to the bedside as we consider treatments is so multi-factorial and multi-complex that all that needs to be brought into consideration. Whenever I walk into the room, I tell residents usually the medical part can be resolved pretty quick, but we’re reading how much we can communicate? What’s the level of understanding? What do I understand about the support system for this person? Is there someone who can drive to the treatment center? Is there someone perhaps whose other medical conditions would create certain challenges in how they’re gonna be treated?

This person is telling me they do daily hikes for four miles. Well, that’s different from someone who I see comes into the clinic and has to use a cane. We try to integrate all of that information to make the right decisions. I’ve made a lot of my career in the early years working and showing how, for instance, genetic factors are important. I’ve come to realize later in my career and through some of the very elegant work that other colleagues have done, that these factors are just as important in determining the ultimate outcome of patients. Whenever I talk about that clinical experience, there’s two things I always tell the residents.

I use the residents a lot because I think it’s a good example of how we aspire to interact with patients. Number one is every single encounter is a final exam. You have to put your best foot forward. Every single encounter should be considered a final exam. Number two is when I walk into that room, there are three things I do, particularly the first time I meet a person.

Number one is connect, right? We cannot have a conversation and I’m not gonna be able to move forward unless we have a human connection and I have gained the trust of the patient and the family members that are there. That’s number one. The second point is decide. That is usually okay, we’re gonna do this treatment or that. That is a small part. Most of the time for me, that’s a very small fraction of the time and of the mental energy that I consume. There’s cases that are more complicated, but most of the time it’s pretty straightforward. So, it’s connect, decide do very small, and then on the other end is explain.

So, that’s how I can connect. I propose we do this, and then why we are gonna do it and what can you expect. If you can do those three things, I think that goes a long way in establishing a fruitful and a productive relationship with a patient and their families.

Katherine:                  

I would suspect that you also take into consideration the patient’s health, their age, maybe test results, side effects, things like that?   

Dr. Fonseca:               

Of course. So, we look at the medical record and with the advent, of course, of the electronic record and all the tests that we do, our consideration is quite complex. We have to look at all those factors, and the age, and comorbidities. It’s rare that we would take one factor alone that would trump everything else. We usually have to integrate the information. The same is true when we manage myeloma patients and we’re monitoring their protein levels and their response to treatment. I tell patients, they ask me, “What would you do? What’s the magic number for this or that?”

I say, “It’s a little bit like you’re flying a Cessna plane and you have all these dials in your dashboard, and that’s how we manage the situation is the integration of all of that information.”

Katherine:                  

Right. Can you help us understand, Dr. Fonseca, how test results may affect treatment options?

Dr. Fonseca:               

Sure. Happy to do that. In myeloma, we are very fortunate in that we have, and it’s not the topic for today, but we have the best biomarker that exists for any cancer. That is that we can measure the proteins that are associated with the growth of the cells. We have multiple tests that we can do. We do them in the blood and we do them in the urine. They’re simple tests that have been done for decades now that allow us to monitor how a person is doing with regards to their disease. I use the following analogy. Myeloma cells live inside the bones, as I mentioned, in the bone marrow.

They don’t come out into the blood. So, we cannot measure them. Indirectly, we can measure how many they are and how they are behaving by measuring this protein. I use an analogy of imagine you’re walking in a street, and you see smoke coming out of a building. There are two things you can do. First is you diagnose that there is a fire inside the building, right? We see that with myeloma by measuring these abnormal proteins.

Then as a firefighting team comes on, you can gauge whether they’re making progress or not by the amount of smoke that comes out. That’s exactly what we do when we monitor myeloma. We monitor the M-Spike, the serum free light chain, the urinary proteins. That’s how we make those determinations.

At the same time, we do that, we have to look indirectly at the rest of the body. We have to look at the kidney function. We have to look at the blood counts. We have to look at the hemoglobin and the red cell count because that can (A) start on the wrong foot because of the myeloma itself, but (B) can also suffer as a consequence of our treatment.

It is, again, that idea of having the multiple dials in the dashboard that allow us to reach our practice. We have to be adjusting. So, if we measure the proteins and we’re doing great, but then at the same time we see we’re suffering in blood counts, and we may need to adjust those as we provide supportive treatment. If we don’t see the proteins go down, then that may mean we need to change to a different form of treatment or that the person is unfortunately a refractory or relapsing to something.

So, that’s how we integrate the test results into our management.

Katherine:                  

What sort of questions should patients consider asking about their treatment plan?

Dr. Fonseca:               

I think it’s important that patients understand a few things. They can be described in multiple ways. Number one is, of course, what? What is it that is being used? I think that includes a description of what to expect, the practicalities, the names of the medications, their side effect profile, and what to report when you use those medicines. I think that’s very important because if you’re empowered with that information, you’re gonna be better off as you react for symptoms that may come along. I always tell patients when you have a cancer diagnosis, your self-awareness goes through the roof because we’re gonna be paying attention to everything, every skin change, every pain we have.

So, I think having a bit of that proactive discussion becomes important as they think about the treatments that they want. I think the how-to on the practicalities are very important. The best where the nursing team and the pharmacists help us a lot too. Do you take the medicines at night? Do you take them with meals? Is there something that you shouldn’t be mixing? How much time would it take for me to get a refill? It’s different to get a medication from a specialty pharmacy versus your down-the-street Walgreens. So, all of those things are important that patients, again, participate in the understanding.

If not them, at least the caregivers that are a part of this team. I think it’s important that patients ask also some brief descriptions of (A) the biology of the disease. If I have myeloma, what type of myeloma do I have? Does that matter as far as what treatments I’m going to be using? What treatment options may be available to me because of my specific subtype? We have subsets of myeloma that have options that are not available to others.

Also, I think it’s important that patients also ask a sense from the physicians as to where they are. I’d like to describe this a little bit more. Sometimes, patients ask us specific questions about, am I in a complete response? Am I in a very good partial response? What is a PFS? Those terms work very well when we talk about clinical trials, but they don’t necessarily describe in a great way the situation for an individual patient. I’d use a lot more objectives than I’d use technical terms when I describe where patients are. I say, “You have an excellent response. You have a very deep response.”

Then I’d provide more details if they want. “Yes, you’re MRD-negative at 10 to the -6.” But sometimes I find that it’s harder for patients to understand where they are if they completely focus on the staging system or the response criteria, etc. Because maybe a VGPR, a very good partial response, doesn’t sound very good.

But then you can be in a very good partial response for 15 years and it doesn’t matter. You my want to be in an MRD-negative status, but you still have a good outcome. That’s why the general description of the status by a physician becomes important.

Katherine:                  

Do you think patients should get a second opinion consult with a specialist?

Dr. Fonseca:               

In general, my answer is going to be yes. This is not self-serving. I think myeloma has become so complex that trying to integrate at least once, or if not, in some infrequent basis, an opinion of a myeloma specialist becomes important. This is no one’s fault. If you’re a community oncologist somewhere where myeloma represents only a small fraction of your practice, I can guarantee you, you cannot stay on top of the literature. I cannot stay up with everything that goes on with myeloma, even though that’s what I do 100% of the time.

I get an email every week with all the articles, all the publications, and I have to integrate that. I have to think, okay, does this matter or not? I go to the professional meetings. I see all the abstracts and I still feel like I’m missing out. How could you do that if that is only a small fraction of your practice? I’m sure that the same applies for other cancers, breast and colon. You can’t move. You cannot uproot yourself and leave your community and your family, but I think there should be ways by which patients at least have an opinion from someone who has more expertise. Fortunately, there are many centers across the nation now that have that expertise for the management of myeloma.

Katherine:                  

Dr. Fonseca, we have a question from a newly diagnosed myeloma patient. Barbara says, “I am just about to begin my first myeloma treatment. What can I expect?”

Dr. Fonseca:

Thank you, Barbara, for the question. I think if you start on treatment, first of all I hope they already went through a good description of what the treatments are, the frequency by which you’re gonna have to go to the center, and also what are the toxicities to look out for.

One of the most common toxicities that we face and one of the most challenging parts of initial treatment is the use of steroids. So, we use dexamethasone as part of every single regimen we use for myeloma. I tell patients, “Dexamethasone is a simple drug at first glance, but it’s oftentimes the most complicated part of treatment.”

The human brain works at triple speed when you’re on dexamethasone. So, it’s hard to sometimes be able to sleep properly. People can become anxious and even the sweetest person in the world can become a little bit edgy on dexamethasone.

I always say Mother Teresa on dexamethasone would be an edgy person. Just be patient. Work with the team. Just know that on the other side of treatment there is a return to normal life.

Our goal as we embark on treatments and, for instance, is I see patients that are going to go through transplant, I tell them, “Our goal is you finish, you recover, and you go back to your life. You back to work. You go back to your family, your kids, your sports.” That’s really what we strive for when we treat patients with myeloma.  

Katherine:                  

Yeah. Once on therapy, how is the disease monitored and how do you know if the treatment is working?

Dr. Fonseca:               

Well, fortunately, we use the same markers. Once a person is in therapy, we will be monitoring. We monitor at least on a monthly basis of those myeloma protein markers. Once a person reaches a great level of response, sometimes we complement that with an analysis of the bone marrow. Of course, it’s more invasive, so we don’t like to do a lot of them, but we do them as needed. As we go forward and monitor patients, we will be looking for signs that those proteins remain in a low level as stable as an indicator that the disease is under control.

Now, if I saw someone and then I start seeing that there’s an increased concentration of those proteins or we see something else clinical, we might need to do a little bit of a regrouping and test again in great detail to determine if the person is experiencing regrowth and the disease is so-called relapsed.           

Katherine:                  

Why is it so important for patients to speak up when it comes to symptoms or treatment side effects?

Dr. Fonseca:               

Well, that’s a great question. If you don’t speak about them, we don’t know about them. It seems very obvious, but then we cannot make the proper adjustments. I’ll give you a couple of examples. I already talked about dexamethasone, but a common drug we use is something called bortezomib. Bortezomib is a proteasome inhibitor.

That’s a mouthful, but it’s one of the key type of drugs we use. It’s given as an injection under the skin. Not to be confused, by the way, with daratumumab. Faspro is the name of that medication, so not to be confused with that is bortezomib, which we have been using for many years.

Bortezomib has a potential toxicity that is called peripheral neuropathy. If patients have peripheral neuropathy, that can go from very mild where you have some numbness and tingling, to the more extreme cases that it’s associated with pain, discomfort, even weakness and disability.

Well, if we don’t know that’s happening, then we can’t react to it and we can’t adjust doses or switch to something different altogether. You can imagine now we have more options, but in the old days, I always tell patients, “You might be tempted not to say anything about this because you might be thinking, boy, this is working. I don’t want to interfere with my treatment. I can live with the peripheral neuropathy.” But if it gets worse, despite the fact that the treatment is working, the person might have a very significant impingement on their quality of life.

More so now that we have so many alternatives, it’s important not to get us into a path that we might reach a point of an irreversible chronic complication from treatment.

Katherine:                  

No, and that would be awful.

Dr. Fonseca:               

Absolutely.

Katherine:                  

Before we end the program, Dr. Fonseca, have there been any recent developments in myeloma treatment in research that make you hopeful? 

Dr. Fonseca:               

Absolutely. I would say that the one area of work that makes me most hopeful is what we’re seeing with immunotherapy. We have seen that both as the ASH meeting, as well as the ASCO meeting in this year, where people are presenting updates with the various clinical trials with either bi-specific antibodies or CAR T cell therapy as a new avenue for the treatment of myeloma.

In fact, at the last ASH meeting, we had 14 presentations of different compounds or different constructs that are active. I think the future is bright in that regard. We’re seeing their application right now. A lot of these updates have also been made as ASCO.

We’re seeing the update of the treatment of treatments with fairly advanced and aggressive disease where we can still show very significant responses. I participate in some of these trials. I can tell you in my institution, using some of the bi-specifics, I see patients who have previously exhausted all of their options and now are MRD negative at 10 to the -6.

If we’re seeing that in the very advanced disease, I cannot wait to see what happens when we start using these treatments in either early relapse and why not in the near future as frontline part of our therapy? I think to me, that whole field of T-cell engagers, where there’s bi-specifics or the CAR T cells remains one of the most exciting areas for future research.

Katherine:                  

How can patients stay up to date on information like this?

Dr. Fonseca:               

I think what we alluded to before is very important to work with groups like yours and other patient support organizations that can keep them up to date. I think they’re doing a very good job at also providing updates post some of the large meetings. I know there’s a lot of patients out there that are very sophisticated that will even join the medical meetings. That happens with some frequency; that they want to learn, and patients that go and ask me details about the statistics of the trial. That’s a whole spectrum, right?

But at the minimum, I would say a strong connection with a support group, or a patient support organization becomes an imperative as you deal with this. Also, that would help you because with this whole concept of the information not always being complete and truthful, that can be scary as well, too.

If someone goes and just looks for, I would say even some of the resources that are out there in a textbook today, just keep in mind that textbook was probably written five years ago, and it represents the studies of about 10 or 15 years ago. How that relates to you, it’s very distant. So, it is because of this continuous process of research that we know better what’s going on at the present time.

Katherine:                  

Dr. Fonseca, thank you so much for taking the time to join us today.

Dr. Fonseca:               

Oh, it’s my pleasure. Thank you for the opportunity.

Katherine:                  

And thank you to all of our partners. To learn more about myeloma, and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us.

Is the COVID-19 Vaccine Safe for Myeloma Patients?

Is the COVID-19 Vaccine Safe for Myeloma Patients? from Patient Empowerment Network on Vimeo.

 Should myeloma patients get the COVID-19 Vaccine? Dr. Joshua Richter encourages all patients to get the vaccine but notes important considerations around treatment.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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Transcript:

Katherine:

Is the COVID-19 vaccine safe for patients with myeloma?

Dr. Richter:

Absolutely, 100 percent yes. Everybody with myeloma should absolutely get the vaccine. What’s a little more complicated is the timing of it. So, one is in relation to stem cell transplant or CAR T-cell therapy. If you’ve had one of these, obviously, consult with your provider. But the general recommendation is to wait about 60 to 90 days after a high-dose therapy like that. And it’s not a question of safety, it’s a question of efficacy. Vaccines are like vegetables, seeds, you have to put them in the ground to grow. If you give yourself a vaccine right after a stem cell transplant, well, your bone marrow is not ready to work with it. It’s like planting a seed in the desert.

You want to make sure your immune system can take in that vaccine and give you immunity. So, you have to wait at least 60 to 90 days. The other question is, what happens if you’re getting continual therapy? And we don’t know the answer for most of these drugs, but one of the things is dexamethasone (Decadron), which is a steroid. Almost all myeloma therapy comes with some steroids. And we like to separate the vaccine from the steroid dose by a little bit if we can. Again, always important to talk with your care team as to risk/benefit about holding certain treatments.

Myeloma Treatment Decisions: What Should Be Considered?

Myeloma Treatment Decisions: What Should Be Considered? from Patient Empowerment Network on Vimeo.

When deciding on a myeloma treatment, what factors affect your choice? Dr. Joshua Richter shares key considerations, the patient role in making decisions, as well as key questions to ask about treatment

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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Transcript:

Katherine:

Dr. Richter, would you please start by introducing yourself?

Dr. Richter:

Sure, my name is Dr. Joshua Richter. I’m an Assistant Professor of Medicine at the Tisch Cancer Institute Icon School of Medicine at Mount Sinai and the Director of Myeloma at The Blavatnik Family Medical Center at Chelsea at Mount Sinai.

Katherine:

Great. Thank you. When making a treatment choice, what are three key considerations for myeloma patients?

Dr. Richter:

Absolutely. So, whenever we decide on treatment options, we consider three main topics: patient-related factors, disease-related factors, and treatment-related factors. So, patient-related factors are easy. How old or young are you? How fit or frail? Do you have any comorbidities, meaning other medical problems like heart disease or diabetes?

Disease-related factors are another important one. How aggressive is your disease? Is it rising up very quickly? Is it very slowly? Do you have something that we call extramedullary disease which means myeloma outside the bone marrow in the mass that we call a plasmacytoma? And that influences how we treat things.

And the last is treatment-related factors. What treatments have you, previously, had, how did you respond to them, and what side effects did you have?

If you developed a lot of neuropathy with one drug, we may not want to choose a drug that continues to have that type of side effect profile.

Katherine:

What’s the role as a patient in making treatment decisions?

Dr. Richter:

The role, from my standpoint of the patient, is honesty. You don’t get extra points for being in pain. I want to hear from you. I want you to tell me what your concerns are, short-term, long-term. I want you to tell me about little problems that you don’t – it’s not that you don’t want to bother your care team, we want to know.

Because something little may mean something big to us. So, all we want is for your well-being. And the better we keep those lines of communication open, the better.

Katherine:

Are there questions that patients should consider asking about their treatment plans?

Dr. Richter:

Absolutely. I think in a day and age where there’s so many different options, I think it’s always important to ask the care provider, what are the alternatives to this? Or why did you select this treatment for me? Because many times, there are alternative answers. So, in myeloma, there are a lot of options that may be good for someone. And the physician team may say we recommend this drug, and the patient may have trouble getting back and forth to clinic for logistical reasons. And there may be an all-oral alternative that if you don’t ask, we may not know that that’s going to be your preference. So, really that dialog is crucial.

What Standard Testing Follows a Myeloma Diagnosis?

What Standard Testing Follows a Myeloma Diagnosis? from Patient Empowerment Network on Vimeo

What tests will you have following a myeloma diagnosis? Are there additional tests you should request? Dr. Joshua Richter provides an overview of key testing for myeloma and why each test is necessary.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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Transcript:

Katherine:

What standard testing follows a myeloma diagnosis?

Dr. Richter:

So, the standard testing that follows a myeloma diagnosis is multifaceted. So, the first one is blood work. And we draw a lot of blood tests to look at the bad protein that the cancer cells make. So, we send tests like a protein electrophoresis which tells us how high that bad protein is. We send immunofixation. That test tells us what type of bad protein it is. You’ll hear names like IgG kappa and IgA lambda.

These are the different types of bad proteins made by myeloma cells. Oftentimes, we’ll send urine tests to find out how much of that bad protein that was in the blood is coming out in the urine. We will, typically, do a bone marrow biopsy. It’s a test where we put a needle into the back of the hip bone to look at the marrow itself. And we’ll use that marrow to figure out how much myeloma there is, any other characteristics like the genetic changes in those cells.

The other big thing is imaging. So, the classic imaging that we do with myeloma is something called a skeletal survey. It’s, basically, a listing of X-rays from head to toe. But nowadays, we have newer techniques, things like whole body low-dose CAT scans, something called a PET-CT scan, and MRI scans. And your care team may have to figure out which one is right for you at what given time.

Katherine:

Mm-hmm. Are there additional tests that patients should ask for?

Dr. Richter:

Absolutely. One of the most important things from myeloma has to do with the genetic risk stratification.

So, for almost all cancers, the staging has a very big impact. And people will often think of cancer in stages I, II, III, and IV, and they’re managed very differently depending upon what stage it is. Myeloma has three stages, stage I, II, and III. But the most important thing is, actually, beyond the staging is what’s called the cytogenetics risk stratification. So, it’s really important when the bone marrow is sent to be sure that it is sent for, kind of, advanced techniques. Because you really want that snapshot of exactly what the genetic profile is, because that gives us information of A) how to treat, and B) prognostic, you know, who will tend to do better or worse based on this information. And even though that may not tell us which drugs to use, specifically, it may say, should we do something like a transplant or not? Should we consider a clinical trial early or not?

Katherine:

I see. How do test results affect treatment choices?

Dr. Richter:

So, test results can affect treatment choices in a number of ways. Probably, the most common one is thinking about the routine blood tests like your CBC or complete blood count and your chemistry, which looks at things like your kidney function. Some drugs tend to have more toxicity to the blood counts. So, if your blood counts are very low, we may choose drugs that don’t lower the blood counts very much.

Kidney function which we, usually, measure by something called the creatinine. Creatinine is made by the muscles and cleared out by the kidneys. So, if your kidneys aren’t working very well, you don’t pee out creatinine, and that creatinine level will rise in the blood. If your creatinine level is high, we may choose certain drugs that don’t affect the kidneys or not metabolized or broken down by the kidneys.

The genetic studies that we use – we’re not quite at this base yet where we can say, if you have this genetic abnormality in your myeloma, we should use this drug except there’s some really great data on the cutting edge about a drug called venetoclax.

Venetoclax is a pill that’s used to treat other diseases like lymphoma and leukemia. And it turns out that people who have what’s called a translocation (11:14) which means part of the 11th chromosome and part of the 14th chromosome in the cancer cells swap material.

Those people respond amazingly well to venetoclax. So, we’re starting to have what we would call precision medicine where we find your genetic abnormalities, not that you got from your parents or passed to your kids, but the genetics inside the tumor cells to tell us which treatments will work best for you.

AML Research Updates: News From ASH 2020

AML Research Updates: News from ASH 2020 from Patient Empowerment Network on Vimeo.

AML expert Dr. Jeffrey Lancet shares the latest news from the 2020 American Society of Hematology (ASH) annual meeting. Dr. Lancet sheds light on headlines from the meeting including FLT3 inhibitor research, combination therapies with venetoclax, a promising inhibitor therapy, and shares his optimism about the future of AML treatment.

Dr. Jeffrey Lancet is Chair and Program Lead in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. He is nationally and internationally recognized for his clinical research in the field of acute leukemias. Learn more about Dr. Lancet, here.

Download Program Resource Guide

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Transcript:

Katherine:      

Hello, and welcome. I’m Katherine Banwell. Today we’ll discuss the latest news from ASH 2020 and how AML patients can advocate for personalized care. Joining me is Dr. Jeffrey Lancet. Welcome. Would you please introduce yourself?

Dr. Lancet:                   

Hi, sure. My name is Dr. Jeff Lancet. I’m at the Moffitt Cancer Center in Tampa, Florida, where I am the Chair of the Malignant Hematology Department. We spend a lot of time treating patients and conducting clinical trials of Acute Myelogenous Leukemia.

Katherine:                   

Okay. Thank you. Dr. Lancet, the American Society of Hematology Annual Meeting just closed. What are the AML headlines from this year’s meeting?

Dr. Lancet:                   

Yeah, so as usual, AML was a very busy area for clinical presentations this year at the ASH meeting focusing largely on novel and targeted therapies.

I don’t believe that there were many practice changing developments per se, but rather discussions about many promising therapeutic strategies that are still under development and moving forward rapidly largely in the areas of targeted therapy, low intensity therapy, measurable residual disease and things of that nature.

Katherine:                   

What does this research news mean for patients?

Dr. Lancet:                   

Well, I think that there’s a lot to be encouraged about and maybe I’ll take the time to review some of the highlights in what was presented with respect to some of the novel therapeutic approaches that many of our patients can look forward to receiving in the not too distant future.

So, we often talk about you know, targeted therapies and, of course, one of the major targets over the years has been that of mutated FLT3 which is one of the most common mutations in AML.

And at this meeting we saw several presentations on clinical trials resolved to utilizing inhibitors of FLT3, with some emphasis on the most recently approved second generation drug called gilteritinib.

There were I thought three major presentations focusing on gilteritinib and one was an update on a randomized Phase III trial comparing gilteritinib plus azacitidine versus azacitidine alone in newly diagnosed unfit for induction chemotherapy patients with FLT3 mutations, preliminarily showing good tolerability and high composite complete response rates in the combination on.

There was another trial of gilteritinib plus venetoclax in relapsed and refractory FLT3 mutated AML.

And what was interesting was that a very high percentage of patients achieved response with this combination of gilteritinib plus venetoclax, many of whom were heavily pretreated previously and many of whom had also gotten prior FLT3 inhibitor therapy during an early stage of the disease. So, the combination of gilteritinib and venetoclax and this more refractive study, it was encouraging to see these promising responses.

And then we saw some data reporting the effects of gilteritinib in combination with more traditional chemotherapy induction with a couple of studies demonstrating both a high complete response rates as well as high rates of mutation clearance of the FLT3 mutation.

So, those were very encouraging data that were presented with respect to the FLT3 mutated AML population.      

So, another very important drug that reached the marketplace for AML recently is a drug called venetoclax, which is an inhibitor of a protein called BCL2.

And this drug was recently FDA approved for use in combination with low intensity chemotherapy drugs such as azacitidine or decitabine.

And it seems as though the combination of venetoclax plus one of these hypomethylating agent drugs, azacitidine or decitabine has resulted in very, very strong efficacy signals as recently published in a New England Journal of Medicine paper that reported on the results of the Phase III trial of venetoclax plus azacitidine.

So, that has now become standard of care for older less fit adults with newly diagnosed AML; the combination of venetoclax plus a hypomethylating agent such as azacitidine.

And naturally, there’s been interest in really kind of taking it several steps further to advance the role of these combinations and to also look at additional drugs in combination with venetoclax plus hypomethylating agent therapy.

So, we saw some of that at the ASH meeting this year. One approach would be to take venetoclax and then to combine it with more intensive chemotherapy for perhaps more fit patients or younger patients that could undergo a more intensive program.

So, we saw presentations of venetoclax being combined with a drug called CPX-351, which is a novel liposome formulation of two common chemotherapy drugs that had been approved a few years ago for secondary AML. And we also saw a combination strategy with venetoclax, and a regimen known as FLAG-IDA, which is a commonly used induction regimen in acute myeloid leukemia.

And I think it’s important to recognize that although these trials that combine the venetoclax with more intensive chemotherapy showed signs of good efficacy with good response rates, there were definitely signals of increased toxicity, hematologic toxicity primarily, which is not completely unexpected with venetoclax knowing that it can cause significant lowering of white blood cells and platelets and hemoglobin.

And then finally, there is a lot of interest in, you know, doing these types of combinations with venetoclax in different subsets of AML and one subset of AML that has been very important recently is that of the IDH mutated AML population of patients.

IDH is a fairly common mutation that occurs either in the Isoform of IDH1 or IDH2 and there’s about a 15 to 20 percent incidence of IDH mutations in AML.

Now we do have an inhibitor for both of these types of mutations: ivosidenib for IDH1 and enasidenib for IDH2, but there also appears to be a strong role for venetoclax plus azacitidine in IDH mutated AML.

We saw from a series of patients presented by a physician at MD Anderson looking at outcomes with venetoclax plus azacitidine in IDH mutated AML. And the response rates were very high when you give HMA plus venetoclax to these patients with IDH mutated AML.

But I think more importantly was that there were what we call high intro patient response rates when switching between venetoclax and HMA therapy with an IDH inhibitor containing regimen.

In other words, a patient would have a good chance of responding to the initial therapy and then if or when that therapy stops working, having a good effect from a salvage therapy with the other regimen. So, when you see initially azacitidine plus venetoclax and then had a relapse, the IDH inhibitors worked well and vice versa if you had received an IDH inhibitor and then subsequently received HMA-venetoclax at a later time point that also worked well.

So, it’s encouraging to see that you can potentially sequence these drugs and get continued responses along the way and ultimately we think will help a survivor and keep patients in a better state of health even longer.               

So, I just wanted to take a few minutes also and discuss some of the newer more novel therapies that are really hitting or approaching the landscape right now. One of these is called CC486, also known as oral azacitidine or ONUREG. And this drug was shown in recent literature to prolong overall survival in patients who are in first remission from their AML who had received induction chemotherapy.

So, this drug was used as maintenance therapy after a variable number of consolidation regimens. And people who got this ONUREG or oral azacitidine drug as maintenance therapy, it resulted in longer survival compared to those who had received placebo.

And this was presented at last year’s ASH meeting, but this year’s ASH meeting provided an update, a very important update, showing that the overall survival advantage from this drug, this oral azacitidine drug, when used as maintenance was independent of whether a patient had measurable residual disease at the time that they went onto the maintenance therapy.

In other words, whether you had MRD, measurable residual disease or not at the time of the study entry, your responses were still more favorable, your outcomes were more favorable, if you received this oral azacitidine drug.

So, this was FDA approved earlier this year for patients in the maintenance phase of therapy for AML who had gotten prior reduction chemotherapy.

And importantly, this drug was also shown to be able to convert about 25% of patients who were positive for measurable residual disease; convert them from positive to negative. So, even though they were in remission, they had measurable residual disease and this drug in about 25 percent of the cases converted that from positive to negative. So, that’s a very important finding as well.

Another important drug that I think you should keep your eye on is a drug called magrolimab. This is an antibody against a certain type of protein that is present on the immune system cell called the macrophage, and when this magrolimab drug was combined with azacitidine in a recent clinical trial, it was demonstrated very high response rates of over 65 percent.

And, in particular, in patients with P53 mutations, which is a very bad mutation to have in most cancers, including AML, in patients with this high-risk mutation, the combination of magrolimab with azacitidine appears to be effective based upon the early data that we have with high response rates.

And then finally, I just wanted to make mention of another important area in, not really just AML, but in all cancer and that’s  outcomes disparities between different races and ethnic groups. And we saw a very important presentation at the plenary session this year where the authors reported outcomes amongst younger patients with AML who were African American compared with Caucasian.

And the data clearly indicated a worse overall survival amongst Black patients compared with white patients under age 60. And this included patients who were enrolled in clinical trials. So, that it appeared that African American patients have a worse outcome than Caucasian patients with acute myeloid leukemia highlighting the need to better understand various risk factors and other factors that play into these disparate outcomes between our Black American population and a white American population, which I think could shed light on additional disease characteristics that may help everybody as well.