cytogenetics Archives - Page 2 of 7

How Does the Presence of Molecular Markers Affect AML Care?

Related Resources:

Does Maintenance Therapy Have a Role in AML Care?

Advances in AML Research: Where Do Clinical Trials Fit In?

Transcript:

Katherine Banwell:

Hello and welcome. I’m Katherine Banwell, your host for today’s webinar. Today’s program is a part of our Insist series. We’ll discuss how to access the most personalized AML therapy for your individual disease and why it’s vital to insist on key testing. Before we meet our guest, let’s review a few important details

The reminder email you received about this program contains a link to a program resource guide. If you haven’t already, click that link to access information to follow along during the webinar. 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. Well, let’s meet our guest today. Joining me is Dr. Ann-Kathrin Eisfeld. Dr. Eisfeld, welcome. Would you please introduce yourself?

Dr. Eisfeld:

Hi, thank you so much, Kathrine. Yes. My name is Ann-Kathrin Eisfeld. I’m currently an assistant professor and hematologist at the Ohio State University.

And I’m also serving as the director of the Clara D. Bloomfield Center for leukemia outcomes research at the James.

Katherine Banwell:

Thank you so much for joining us today and taking the time to discuss this important issue. To set the stage for today’s discussion, Let’s start with this important question. How would you define personalized medicine as it relates to AML care?

Dr. Eisfeld:

I define personalized medicine in AML as have a complete testing at time of diagnosis that consists of not only the morphology of the bone marrow, but we call immunophenotyping, which is looking at the surface markers, but also full review of all the chromosomes, which is called cytogenetics. And with those metaphase testing, I’m looking really at all of them and at the hot spots, which is done by a technique called FISH.

And then most importantly, for personalized testing, it also needs to consist of testing the most common, recurrent gene mutations. Changes in the tumor DNA that we know are contributing to the disease biology and also to the response of the leukemia to different genes.

Katherine Banwell:

Thank you for that, Dr. Eisfield. That helps guide us as we begin our conversation.

I imagine that personalizing therapy for a patient requires a number of tests and then thorough review of the test results. Could you provide an overview of the tests necessary to help understand a patient’s specific AML?

Dr. Eisfeld:

Yes. Absolutely. There are multiple things that go in. And let me –even before we go into the tests – point out one thing. Because as we talk about individualized care – and it is also important to keep in mind that it will be also dependent on the age and of the performance status of the patient.

Because we know that all the changes that are going to be reviewed might be more or less severe depending on really the age of the patient we are discussing. The most critical aspect for every AML patient is a bone marrow biopsy and a bone marrow aspirate on which the testing that I have been referring to are performed.

One, it gives us information about how the – after review of the hematologist, it gives us information about the specific kind of the leukemic cell.

And very importantly – and this is a very more recent development that we know about that’s important. It also tells us whether the acute leukemia is really happening as an acute leukemia or whether the patient without knowing it before might have had a precursor issue. And this is something that by now really in just about half a year we can use in addition to direct treatment.

So, it seems like an ancient thing that we think that the microscopic review is important. But that is one part of it.

The second part – and this is, again, all based on the bone marrow biopsy. The inspection of chromosomes, as I mentioned, may be called cytogenetics. This test takes longer. It sometimes takes up to two weeks to result. And similar, looking at the tumor DNAs and mutations that is done either if you’re at a large institution such as Ohio State or other cancer centers. It’s done in house. Whereas at smaller institutions, it would be done by a sent-out testing that has these recommended gene mutation testings done. And some of those result just within a couple of days.

And these are – but we can talk. And I know we are going to talk a little bit more about it later, but we now have targeted therapies available. This is a really super exciting topic we couldn’t have talked about just even five years ago. And those mutations and those DNA changes come back usually within three to five days.

So, that we are able to decide on treatment.

Katherine Banwell:

How can someone ensure they’re getting an accurate diagnosis?

Dr. Eisfeld:

That’s a very good question. I think the most important part is to go to somebody who has seen acute leukemias as a living. It is a very rare cancer as you know. And if you are seen even by a general oncologist who might be a fantastic oncologist, he might just see one or two cases per year. And thus, might not be up-to-date on the newest recommendations. So, I can just advise anybody – even if he lives further away and trusts his physician a lot – to – for the diagnosis and for treatment planning, come to a comprehensive cancer center, at least for a therapy planning. Because what is now possible is many of these treatments is that we can just give advice.

And then you can still receive treatment in some cases really back at home. But be sure the testing was done correctly. And really give you every option to take into consideration what the best treatment would be for you, what the best treatment is for the patient. Having this trip – which can be hours of a drive. And I appreciate this. Having that done once would be, I think, the best thing to do.

Katherine Banwell:

Many cancer types are typically staged. But that’s not the case with AML. AML is often considered low risk or high risk. Is that right?

Dr. Eisfeld:

Yes. And we – I think that’s very well how you put it. And we can even – they even add an intermediate risk by now to it. And I love this question because that’s what I like to study or what I’m studying here. The one important thing to keep in mind – and this is something even many hematologists don’t think about is that the risk assignment of acute leukemia, of AML if you think about it as low, or high, or intermediate risk is risk – or is actually better said not risk, but chances to respond to conventional chemotherapy. So, the way all this was defined is that if you have, for example, a multitude of chromosomal abnormalities – as you call it complex karyotypes – it would be considered adverse. This means your chances of responding to the standard of care in terms of chemotherapy are very, very low.

And similarly, if you have other changes such as a NPM1 mutation, your chances are considered very high. And but – so, the risk assignment with the increase of treatments now changes. We still also – and when I look at that, I think about it in the same way. But in my mind, if I’m talking to a patient, I’m trying to make sure to say, this is considered an intermediate or adverse risk.

But this means that I would not, at the first place, consider you for a standard chemotherapy but rather advise you to participate in a clinical trial or have an alternative care. The second implication especially for younger patients would be to – if you’re intermediate or adverse risk, that you would routinely be considered for bone marrow transplant or stem cell transplant.

Katherine Banwell:

Okay. So, what does it mean to be high risk then?

Dr. Eisfeld:

It means that your likelihood of going into remission – the standard of care is very low. This means – I mean, in very practical numbers, it might be as low as 20 or 30 percent. This meaning getting the leukemia into remission, there are very important differences. The first step at every time in the same high risk means if the patient receives the treatment, how high are the chances that we can get rid of the leukemia?

The second question is how high are the chances once it’s gone that it stays away? Or how high are the chances of relapse? In adverse risk most cases, it’s both – a combination of those. The chances of going into complete remission are lower and the chances of it coming back are higher. So, we have to be very aggressive. This means that we have to consider alternative treatment options. And even if we are then lucky and achieve remission, that we might have to move to more intensive additional treatments such as a bone marrow transplant.

Katherine Banwell:

Dr. Eisfeld, the landscape of AML has changed significantly in recent years. How have advances in testing improved patient care?

Dr. Eisfeld:

It is a different world, Katherine, honestly. I mean, I started practicing in hematology in taking care of AML patients back in Germany actually in the year 2007.

Back then, there was no other testing that was available. All we were guiding and all that we had available was morphology and cytogenetics. And very often, it was very inaccurate. And we also only had two treatment kinds available. One was intensive chemotherapy, and one was something that was just a little bit better than best supportive care. So, many patients could not receive treatment. And the increase in knowledge that we have on a molecular level in AML really did two things at once. On one, we understood we had a more fine tuned understanding on which patients would respond. And the second thing is that this knowledge about the molecular landscape enabled us to have new treatments available that are sometimes in pill form that can target specific mutations in patients who carry these genetic changes.

Katherine Banwell:

Should all AML patients undergo in-depth testing like biomarker testing or cytogenetics?

Dr. Eisfeld:

Yes. Every patient should do that. It can make the difference between life and death. And it can make the difference between receiving – having a hospital stay of four weeks with intensive chemotherapy versus taking the pill at home. This is very rare that this is possible. But it is possible. And of course, you – one would not want to miss this chance if it would be possible.

Katherine Banwell:

With all the new tools that are available, what other factors do you consider when working with an AML patient to choose a treatment approach for them?

Dr. Eisfeld:

The most important aspects are what we call – and this is – I’m glad that you bring this question up because I feel you have to think of – and that was what we’ve been talking about – called disease-associated factors. This is everything in the leukemic cell. They – how does a leukemia looks like? How does the blast look like? What changes are there?

That’s the biggest part of what I would call patient-associated factors: the patient age, the patient performance status, actually the patient. In every – because I think, sometimes, we forget about it. But we just look at all the molecular testing.

But even if – for example, there would be a patient with a very good risk leukemia, where I think, “Oh, this leukemia should respond very well to an intensive chemotherapy.”

If the patient cannot tolerate chemotherapy or – and I see it more often than I would wish for patients who are young who have a great performance status, but they just cannot – they – their family reasons. Small children sometimes – they just cannot be away for so long. This all comes into consideration. So, it’s really important because we all work together as a team. And the right treatment for the leukemia might not be the right treatment for the patient.

And for most cases, however, I think, it will only work if one stands with a whole heart with those physicians, and patients, and family. Because it’s a long journey behind the care that’s being given. And so, this is a joint decision-making, and there are different options that can be done. Of course, I would not advise something where I would think there are no chances of success.

And so, this has to be an open discussion. But this is – it’s very often a very tough treatment to communicate that and see what are the goals of each patient? That will be most important for treatment and decision-making.

Kathrine Banwell:

Dr. Eisfeld, we’ve been discussing treatment choices and how they vary for individual patients. What types of AML treatment classes are currently available?

Dr. Eisfeld:

This is a very good question. The most classic treatment class is intensive chemotherapy. This is just because people might have heard the names. It is called 3 + 7 or 7 + 3, which refers to one weeklong impatient chemotherapy treatment. But you get one chemotherapy for seven days. And the first three days, you get a second treatment as well.

That’s why it’s called three in seven in here, but it’s a total of seven days. So, we have intensive chemotherapy. And there are different flavors of it. But this is usually the backbone. The second class is what I would call a targeted inhibitor. And here we can look at two different aspects. We have target inhibitors for a specific DNA mutation that are found. And specifically, one are called IDH or FLT3 mutations.

And these are pill forms that I usually by now combined with a third drop class which is called hypomethylating agents. And I will go through in a moment.

But these are pills that really only work in patients and carry that genetic change. They have very, very low toxicity and very high chances of working. So, that’s why this testing is so important to see if one is one of the 15 percent of AML patients carrying an IDH mutation – 15 percent isn’t low. And a similar rate carries a FLT3 mutation.

And then there is also going to target inhibitors. That is targeted because it is against what I would call a pathway. The gene that is commonly activated in acute leukemia – and this is called BCL-2 and the drug is called venetoclax (Venclexta).

This is now stormed through the acute myeloid leukemia world in just a few years ago and has been approved as a front-line treatment option for several patients, especially for those who are older. And we know that even patients who respond usually favorably to chemotherapy, some of those also respond well to venetoclax the Bcl-2 inhibitor. The benefit is that this treatment in many cases if it works, can be done as an outpatient in here and has very often lower complications.

It is actually has so good results that I – sometimes it seems too easy. So, we actually advise patients to still try to get – the first time they get the treatment, do it at a center where it’s done more commonly. Because it sometimes – don’t underestimated the power of a pill. And it’s still a very, very powerful drug. So, doing it in a controlled setting – because if cancer cells break down, they break down and can create all sorts of trouble.

So, that is really something – for several leukemias, it can be concerning. And again, now the treatment group would be called hypomethylating agents. The names are azacitidine (Vidaza) and decitabine (Dacogen). And they act in a very different way. They try to change the epigenetics like methylation patterns. And often, if it is an untargeted way of the tumor cells and they can be used alone.

Or very often by now in combination with the targeted inhibitors that I was just mentioning. These are infusions that can be done either over five, seven, or 10 days depending on the combination treatment. And for patients, as I mentioned before, that don’t respond well to many other options to those patients with a complex karyotype. This is, for example, a scenario where patients can just receive this as their only therapy.

Katherine Banwell:

What about stem cell transplant? You didn’t mention that.

Dr. Eisfeld:

Yes. That would be the next one. So, stem cell transplant always comes as an option, which I would call as a maintenance therapy. Again, two aspects. We have two different end goals.

First is get rid of some leukemia. Second is to make sure it stays away. And as soon as the leukemia is in complete remission, depending on the performance status – the agent. Again, in multiple different things. It’s not an easy decision.

At that time, there has to be a conversation. And that always involves a leukemia physician and a transplant physician very often. These are different providers that goes for the risks and benefits. Where the question is if I only continue to do chemotherapy – because it’s never only once. You would always have to repeat your chemotherapy. What is the likelihood that the leukemia comes back, and does it outweigh the risks that comes with the stem cell or bone marrow transplant that comes in here. But for many leukemias, especially for young patients and for patients with higher risks, this is the only chance of a cure. That is the most curative and only curative attempt for many leukemia attempts.

Katherine Banwell:

Where do clinical trials fit into the treatment plan?

Dr. Eisfeld:

That is the absolute backbone. We always have to think about that.

Everything – all the treatment options that I mentioned – have been clinical trials, just very, very short time – very few years ago. So, every patient that comes to a leukemia or a cancer center, clinical trials will be discussed if they’re available. Because they will provide a special opportunity to have even more fine-tuned treatments – either newer agents. And I think what is very important to mention is that all clinical trials that are available would give the option of the best standard of care. And then the hope that a patient wouldn’t be getting any of the best standard of care options that are approved. The hope is that the new agent or added agent in many cases would even do better.

It’s also important that there’s a lot of additional monitoring during the trial. I think it can be seen in two ways as two parts of a coin. In one way, it may be additional visits to the hospital or additional blood draws that are necessary to be sure that the medications are safe, and that researchers and conditions can learn about it. But on the other hand, it also gives you this extra bit of being looked after and really getting checked in and out, making sure that all organs are functioning that everything is just going fine. And many patients appreciate this a lot. And they have this pair of extra eyes on them all the time.

Katherine Banwell:

Dr. Eisfeld, what therapies are available for AML patients who relapse or don’t respond to initial therapy? And is this treatment approach different from those who are newly diagnosed?

Dr. Eisfeld:

Most of the time, the treatments available at relapse are the same available at the first diagnosis. Just because we know now that, for example, if you have a molecular marker that, for example, is available, it would act with also relatively high chance of relapse upset. However, at relapse, the most important thing I personally would do is consider a clinical trial even stronger than in the first mindset.

Because it means that the leukemia outsmarted current treatments very often. So, usually what we would be doing is see if there is a targeted inhibitor or a cell mutation FLT3 or IDH, which I would personally always prefer to go in MLL rearrangement now for the new menin inhibitors where one would go with the same option as if it would have been their diagnosis. But if not to really consider clinical trials is a strong urge.

Katherine Banwell:

Should patients or should relapse patients undergo genetic testing again? Is it necessary?

Dr. Eisfeld:

Yes. At any time. Yes. Because we know that the leukemia changes. And you just can think about it in the way is that the cells that are surviving treatment, they’ve become smart. There was so much poison. There was so much treatment put on them.

And the ones that survive might have a quiet additional chromosome change as additional gene changes. And even if a genetic change has not been present at time of diagnosis, the reason the cell has survived might have been that it has now one of these changes that came up on a later time during treatment or while the cell is hiding somewhere to come back.

Katherine Banwell:

Are there therapies in development that are showing promise for patients with AML?

Dr. Eisfeld:

There are so many of those. It’s hard to count. And this makes me very happy. There are exciting and again, targeted drugs.

Once drug class is called menin inhibitors, which we – which were just published that show high promise.

And again, very difficult to treat several groups of patients who harbor chromosome changes in MLL genes in here. So, that is a very exciting option.

And there’s very exciting treatments with respect to what you call antibodies – monoclonal antibodies that protects the surface proteins that are being checked regularly. And one of those, for example, is called magrolimab. And that has even promise in these high-risk leukemias or adverse risk leukemias.

And then we are not there yet, but I’m sure we will be in the not too near future. There are also multiple trials that are looking at what we call CAR-T cells. But patients might have heard about for lymphomas or acute lymphoblastic leukemias. AML is a little more tricky with respect to those.

But we’ve seen pre-clinical studies that look really exciting. And I think it’s just going to be just a little more fine-tuning to make those easier, available, and more targeted for AML patients. And I’m very much looking forward to seeing those come more onto the market.

Katherine Banwell:

You mentioned the new menin inhibitors. Who are they right for?

Dr. Eisfeld:

We try to find out more, but definitely for patients that have been shown to be beneficial for patients who have chromosomal and rearrangements of the MLL gene or KMT2A gene. And there’s also good data on patients who have NPM1 mutations.

Even though we know – and these are mutations who harbor this kind of genetic change – have now a plethora, which is a great, of treatment options.

Because we know even conventional chemotherapy has been working decently well in them. We know that venetoclax also is supposed to work very well in them. But again, the data on the menin inhibitor with respect to NPM1 mutations is very exciting.

Katherine Banwell:

So, Dr. Eisfeld, we’ve covered a lot of information related to AML care. As a researcher, what other topics are currently top of mind for you in the field of AML? What are you passionate about?

Dr. Eisfeld:

Again, so many parts. I think there are probably three main things that I’d like to name. And I think about it as a little bit outside the box. Most of what we know about AML, we have become so much better. It’s because we have been studying patients who were treated over the past decades on clinical trials and very often here in the U.S. or in Europe.

But all clinical trials have a bias in that most of them have been done A) on patients who are younger than the age of 60. And B) fewer patients of other races and ethnicities included. And had patients not included that have AML, for example, not only in the bone marrow but on extramedullary sites – how we call it – up to 10 percent of their patients. And also, very often have not been done on very old patients where the AML is very common. So, all the patients – patients from other race, ethnicities, or underrepresented minorities, and patients who present with extramedullary disease are currently in my – underserved.

And these are exciting areas and opportunities of research and of active clinical practice. Because those are the patients we need to include if it’s possible now to include them in clinical trials.

If there are no trials available, then make sure any other additional molecular testing it done to understand them better and to advance our disease knowledge that we make sure that we can give the best possible care.

Katherine Banwell:

I think that the most important part is to get the molecular testing, and to enroll into clinical trials, and then to very often biobanking.

Why am I saying that is because our knowledge AML comes from patients who donated some tissue so that we could learn – researchers decades ago could learn about the genes. We know that leukemias differ so much in between patients.

So, I am worried that we are yet missing out on potentially important genes that need to be discovered and where we could develop docs for. This will only be possible with these additional testing.

The second part is to really consider going to larger treatment and larger treatment cancer center. And there are support systems in case that can help in here.

And the third part is to get involved even as early as possible even if you’re not personally affected, with Be The Match – with bone marrow transplant because there’s a paucity of donors, of people of color that makes it harder for these patients to get a potentially curative treatment in here.

We have other options now in bone marrow transplant where one can use only half-matching donors and or other availabilities. But again, that doesn’t outweigh that the bone marrow and donor registry that we need to get better at.

And I can – there are just so many factors – such a high degree of structural racism that affects people from every corner. And I think we as physicians, as society, and everybody need to acknowledge that. And we have to make sure that we get better to, again, give every patient the best care and keep the patient in mind and see what’s right for them at the right moment.

Katherine Banwell:

Where can patients or people who are interested find out about being a donor?

Dr. Eisfeld:

There is the website called “Be the Match” that one can put in. This is probably the best way to get first information.

And usually, at all the cancer sites. And sometimes, there is information at lab donation places, universities, either or the American Red Cross.

Usually those places have information laid out there as well.

Katherine Banwell:

Dr. Eisfeld, before we close, I’d like to get your thoughts on where we stand with progress in the field of AML. What would you like to leave the audience with? Are you hopeful?

Dr. Eisfeld:

I am incredibly hopeful. I hope – when I started working in hematology, as I said at that time, it was just about when imatinib (Gleevec) came out. Which is this CML pill that really revolutionized care. And so, at that time, I would be – all patients on that bone marrow transplant service had chronic myeloid leukemia. And because they all had to undergo bone marrow transplant. Then Gleevec came, and today, there are no such patients who are see or very rarely that require such intensive care.

So, I am very hopeful that in my practice time, which hopefully –and even earlier on – that there will be a time where we find targeted therapies for almost all patients.

Katherine Banwell:

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

Dr. Eisfeld:

It’s an absolute pleasure. And if there are ever any questions, please feel free to reach out. For patients who reach out, we are there to talk to all of you and give advice as good as we can or put you in contact with the right people.

Katherine Banwell:

Thank you. And thank you to all of our collaborators. To learn more about AML and to access tools to help you become a proactive patient, visit powerful patients.org. I’m Katherine Banwell. Thanks for joining us today.

BIPOC Patients Living With AML | Mortality Rate and Favorable Genetics

February 1, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Experts, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

BIPOC Patients Living With AML | Mortality Rate and Favorable Genetics from Patient Empowerment Network on Vimeo.

How can acute myeloid leukemia (AML) disparities be addressed in BIPOC groups? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center shares insight. Learn about disparities, molecular profile cytogenetics, and clinical trial benefits.

[ACT]IVATION TIP from Dr. Daver: “Clinical trials are usually developed to improve and move forward the standard of care to better outcomes, as well as knowing that there are many different approaches to getting financial support through different organizations, entities and even potentially through some of the clinical trials, as well as considering becoming volunteer donors for national marrow donor programs, so you can support potential transplant for patients from those communities, which will give them a potential curative option.”

Download Resource Guide en español

See More from [ACT]IVATED AML

Related Resources:

Long-Term Effects Acute Myeloid Leukemia Patients Should Know

What Are the Latest Acute Myeloid Leukemia Therapies?

What Different AML Subtypes Are More Prevalent in Certain Demographics?

Transcript:

Art:

Dr. Daver, non-Hispanic Black and Hispanic patients with AML have higher mortality rates than non-Hispanic white patients despite more favorable genetics and younger age. How can we address disparities in AML among diverse patient populations?

Dr. Naval Daver:

This is a great question, and then something that I think we all need to spend more time with understanding, and now researchers started to look at the differences in molecular profile cytogenetics presentations among different ethnic backgrounds. It is definitely true that access to care has been more limited in some of these populations that you mentioned, including the Hispanic population and in the non-Hispanic Black population, and I think there are a number of things that may be causing this issue, so I think one there is definitely an economic divide, and especially for large academic centers where patients do have to travel, often stay locally for a period of time to go on the trial, this causes expense, and a lot of times,I think a number of these populations may not have had funding or they may not have the insurance that would cover that particular center.

And so this is one of the big hurdles… second, I think that there is among us communities, sometimes more suspicion or circumspect approach to clinical trials and large academic centers thing, that’s something that hopefully we will be able to change with programs such as the and many, many others that we all are working on, because I think we actually do want to have more inclusion in clinical trials. And we do want to have a more representation of the entire population rather than just a subset.

So hopefully the understanding that clinical trials are usually done with the intent to improve the current standard of care, and randomization includes the current standard of care, and then something that we think could be added to further improve that, and often that many of the clinical trials may even be able to provide some degree of financial support for travel stay.

These could all help maybe some of these populations to access and get on clinical trials, which is one of the big goals for MD Anderson and other large academic centers and investigators such as myself.

I think the third big hurdle, of course, is that even proven extensive transplant, which still remains the most effective long-term curative approach, we don’t have as many donors for the Black and the Hispanic community proportionately than we do for the Caucasian white population.

So I think this is another kind of call to voluntarily consider becoming a donor for the national marrow donor program, for others who are in that community, because we often do find challenges finding ideal donors, and this is a very simple procedure where it…here one, all you have to do is give us a saliva swab, mail it in.. You don’t even have to go to the clinics.

Nowadays, they log it in and if you’re ever called on, it’s just a blood collection, it’s like donating in blood, and you could save somebody’s life to be probably the easiest thing to save, somebody’s like that you will have the opportunity to do in your life.

So I think it’s really, really important that those communities also start signing up and becoming voluntary donors, so I think these are three of the kind of hurdles, of course, there are many, many others, but hopefully with the big push and impetus that’s happening across the world and across the country and across the large academic centers. In the next five to 10 years, we will see more inclusiveness and more representation of all populations proportionally in the ongoing trials and publications.

My activation tip for this is understanding that clinical trials are usually developed to improve and move forward the standard of care to better outcomes, as well as knowing that there are many different approaches to getting financial support through different organizations, entities and even potentially through some of the clinical trials, as well as considering becoming volunteer donors for national marrow donor programs, so you can support potential transplant for patients from those communities, which will give them a potential curative option.

Share Your Feedback About [ACT]IVATED AML

A Look at Treatment Strategies for High-Risk AML Patients

February 1, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Experts, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

A Look at Treatment Strategies for High-Risk AML Patients from Patient Empowerment Network on Vimeo.

What acute myeloid leukemia (AML) treatments are available for high-risk patients? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center discusses various mutations, potential for cure, and clinical trials. Learn about the outlook for high-risk AML treatments.

[ACT]IVATION TIP from Dr. Daver: “The best way to get up to these agents is to go on clinical trials and incorporate these therapies, both in the frontline setting as well as in the relapsed refractory setting.”

Download Resource Guide en español

See More from [ACT]IVATED AML

Related Resources:

What Are Some Clinical Predictors for Relapse in Acute Myeloid Leukemia?

Assessing Untreated AML Patients Who Are Ineligible for Intensive Chemotherapy

What Does Triplet Therapy in AML Mean for the Future?

Transcript:

Art:

Dr. Daver, what treatment strategies are available for high-risk AML patients?

Dr. Naval Daver:

High-risk AML patients includes a group of a number of different mutations, and cytogenetic abnormalities, this includes TP53 mutation, as well as adverse cytogenetics, which includes chromosome 17, deletion 5, deletion 7, as well as complex carrier type. This entire group historically had a poor outcome and has had limited responses to traditional intensive chemo, even if we achieve responses there, usually short-lived.

We do have some patients where we are able to achieve remission with intensive chemo or with azacitidine-venetoclax (Vidaza-Venclexta) and transition and transmission them transplant with about 25 to 30 percent potentially achieving a long-term remission and possible cure.

But aside from that, there is very little potential to cure these patients with just traditional intensive chemo, venetoclax in this area, there has been developments with the emergence new class of immunotherapy drugs, called CD47 antibodies, the one that’s most advanced in this field is a drug called magrolimab, and we are evaluating the drugs such as magrolimab in combination with azacitidine as well as in combination with azacitidine-venetoclax and are seeing high remission rates, both in TP53 mutated and TP53 wild type.

So this pathway that works by activating a macrophages or the immune system to attack the tumor cells, seems to be in some way mutation agnostic with response rates being maintained even in the traditional high-risk subsets, especially such as TP53 and complex cytogenetics for some of the other high-risk groups such as MLL, we’re using targeted therapies like menin inhibitors, and these seem to work well in those patients who have these adverse cytogenetic molecular abnormalities, so there is progress, and we think that the CD47 antibody field and hopefully the main inhibitor feed will be able to improve outcomes in these traditionally molecular cytogenetic subsets.

My activation point related to this question is for high-risk mutations and cytogenetic commonalities such as TP53 complex carrier chromosome 17 MLL, best hope at this time is in clinical trials evaluating novel therapies such as CD47 antibodies and menin inhibitors. These are not yet FDA-approved, but based on emerging data from the ongoing Phase I, II studies, we think that there is a good chance they will be approved in the future.

However, this time, the best way to get up to these agents is to go on clinical trials and incorporate these therapies, both in the frontline setting as well as in the relapsed refractory setting.

Share Your Feedback About [ACT]IVATED AML

What Different AML Subtypes Are More Prevalent in Certain Demographics?

February 1, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Experts, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

What Different AML Subtypes Are More Prevalent in Certain Demographics? from Patient Empowerment Network on Vimeo.

Are some acute myeloid leukemia (AML) subtypes more common in some demographic groups? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center discusses different forms of AML. Learn about the extent of knowledge about AML subtype demographics.

[ACT]IVATION TIP from Dr. Daver: “Patients, when they transformed what we call secondary AML or MDS, seemed to have a higher predilection for certain high-risk communications such as TP53, and these are best treated with ongoing frontline clinical trials at large academic centers.“

Download Resource Guide en español

See More from [ACT]IVATED AML

Related Resources:

What Are the Latest Acute Myeloid Leukemia Therapies?

How Can We Address Disparities in AML Among Diverse Populations

What Does Triplet Therapy in AML Mean for the Future?

Transcript:

Art:

Dr. Daver, what are the different subtypes of AML, are various subtypes more prevalent in certain demographics?

Dr. Naval Daver:

The main way we have classified AML has actually been changing, so when we talk about subtypes there are actually two different classification systems like WHO and the ICC or ELM classification system. Traditionally, we have been using the ELM for prognostic classification of AML, this divides patients into three major buckets, what we call a favorable intermediate and adverse, and these are based on the underlying chromosome cytogenetics abnormalities and molecular or next-generation sequencing profile of the patients.

In general, in AML there has actually been limited data and publications regarding the demographic distribution, whether it’s regional or racial or cultural, one of the things that we do know, for example, in acute lymphoblastic leukemia is that in the Hispanic population, there seems to be higher frequency of things like FLT3-positive ALL.

But in the AML population, there actually does not seem to be, at least based on published data, huge differences in the molecular or cytogenetic presentation. We have seen some data from different countries that there may be a difference in the prevalence of communications across different regions. For example, in Japan, we do see that the incidence of FLT3 and NPM1 appears to be lower than what has been reported in the United States.

Also, we see in Europe and United States, the incidence of these mutations with FLT3, NPM1 is similar, and then we are seeing in some of the larger academic centers in the U.S., there is an enrichment of referral of patients with TP53, which is very adverse and most difficult to treat mutation, and a lot of that we think is because patients with solid tumors and with other hematological malignancies are surviving longer with the CAR-T therapies, immunotherapies, and because it is over time, they have a risk of developing second AML, which is enriched for TP53 mutation, so we do see over the last two decades that from TP53, which used to be about 5 percent to 10 percent, is now up to 20 percent to 25 percent of AML and growing in proportion because it’s better survival and solid tumors and lymphomas.

The activation tip related to this question is that in general, they don’t review discrepancies based on geography and race, and region in the molecular cytogenetics. However, we do see differences in patients who have received prior chemotherapy, radiation therapy, AML therapy for other solid tumors and lymphoma.

These patients, when they transformed what we call secondary AML or MDS, seemed to have a higher predilection for certain high-risk communications such as TP53, and these are best treated with ongoing frontline clinical trials at large academic centers.

Share Your Feedback About [ACT]IVATED AML

How Is Myeloma Treatment Response Measured?

December 12, 2022/in INSIST! Myeloma, MM Insist Testing, MM Newly Diagnosed, MM Programs, MM Testing, MM Videos ND, MM Videos T, Multiple Myeloma /by Kara Rayburn

How Is Myeloma Treatment Response Measured? from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Betsy O’Donnell reviews the terms that define myeloma treatment response, such as complete remission (CR) and partial remission (PR). Dr. O’Donnell goes on to discuss the new tools that are being used to monitor treatment effectiveness, including MRD (minimal residual disease).

Dr. Betsy O’Donnell is Assistant Professor of Medicine at the Dana-Farber Cancer Institute specializing in Plasma Cell Disorders.

How Is Relapsed or Refractory Myeloma Managed?

Related Programs:

$How Is Relapsed or Refractory Myeloma Managed?$

How Are Patients on Myeloma Maintenance Therapy Monitored?

Understanding MRD and What It Means for Myeloma Patients

Transcript:

Katherine Banwell:

Dr. O’Donnell, Alex wrote in with this question. “What is the difference between a complete response, VGPR, and PR as it applies to prognosis and maintenance after an autologous stem cell transplant?” And before you answer the question, would you define VGPR and PR for us?

Dr. Betsy O’Donnell:

Sure. So, we have different criteria that help us understand how well a drug is working, and they’re uniformly used across clinical trials so that we’re all speaking the same language. And so we talk about a PR, a VGPR, and a CR. So, a CR is a complete response, which is 100 percent of that monoclonal protein that we initially detected is gone. We can’t measure it. Or if you have an elevated light chain, which is another piece of the protein, that has gone back down to normal.

Taking that a step further, astringent CR is if we do a bone marrow biopsy and we can’t find any cancer plasma cells in there. A VGPR is where we see a 90 percent reduction in the amount of protein we can measure, and a PR is anything over – a partial response is anything over 50 percent.

So, that’s a language we speak really just so that when we’re interpreting clinical trials, we all are using the same criteria.

And so these are different terms that classify it. If the example that you gave, someone’s had a transplant, what would typically happen 100 days after that transplant is a patient would restart maintenance therapy.

The classic maintenance is just lenalidomide (Revlimid), which is the pill that they were probably taking before that. And there’s a lot of controversy now but no good answers about changing therapy after a transplant, if you haven’t received a deep response.

What we do know is that after a transplant, when someone goes on lenalidomide maintenance, they continue to respond. So, the greatest depth of response is not necessarily achieved in the induction phase or right immediately after transplant, but over time on maintenance.

There’s another tool that we’re now using and incorporating, both in terms of how we assess treatment but also potentially in how we modify treatment, which is something called minimal residual disease, MRD, which goes a step beyond. When people have astringent CR, a CR, looking for really just traces of the disease on a molecular level.

And all of those help us understand how well the patient has responded and how long that remission might last, but they’re not definitive in terms of how we should adjust treatment based on those right now.

How Is Relapsed or Refractory Myeloma Managed?

December 12, 2022/in INSIST! Myeloma, MM Insist Treatment, MM Newly Diagnosed, MM Programs, MM Testing, MM Videos ND, MM Videos T, Multiple Myeloma /by Kara Rayburn

How Is Relapsed or Refractory Myeloma Managed? from Patient Empowerment Network on Vimeo.

Drs. Irene Ghobrial and Betsy O’Donnell discuss next steps if myeloma relapse occurs or the disease doesn’t respond to treatment. The experts review the necessary tests following a myeloma relapse and how a treatment choice is determined.

Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Learn more about Dr. Ghobrial.

Dr. Betsy O’Donnell is Assistant Professor of Medicine at the Dana-Farber Cancer Institute specializing in Plasma Cell Disorders.

What Tests Are Essential Before Choosing a Myeloma Treatment Approach?

Related Programs:

What Are Currently Available Myeloma Treatments?

How Do Test Results Impact Myeloma Treatment Options?

Transcript:

Katherine Banwell:

We know that relapse can happen. Dr. Ghobrial, how common is relapsed or refractory disease?

Dr. Irene Ghobrial:

Yes, and, fortunately, we do have amazing remissions. We have very long remissions. Many people are living 10 years, 15 years and longer, which as Dr. Nadeem said, was not something we knew about years ago. I trained 20 years ago as a fellow, and myeloma was a survival of three to five years.

We’ve come a long way, but we want to change that even better. We want a cure. We want to tell a patient, “You are done. You’re cured,” and we will not stop until that happens. So, when people have a progression again or relapse, then we want to consider what is the next available option. What is the best option to give them yet one more long, long remission? We are failing sometimes, and that’s because the disease is so bad, the biology of the disease is so bad, and the drugs that we’re using may not be the best drugs for that patient.

And that’s why we need to understand better the biology and pick the right drugs for the right patient up front as much as we can, and also think about earlier treatment. We were just saying we probably have amazing drugs, but we’re waiting way too long until people have almost metastatic disease, and then we treat them. Why not think of an earlier interception when the disease is less mutated, when you have less cancer cells, a better immune system, and use your best drugs then? And hopefully we will achieve cure in many of those patients.

Katherine Banwell:

What testing takes place after a relapse? Is it different than what has happened before, the testing that was done before?

Dr. Irene Ghobrial:

No, the same tests exactly. We sort of say it’s restaging. We check everything again – the bone marrow biopsy, the FISH, because you may now develop a 17p that was probably there, but the very, very small number of cells that you cannot detect, and now it grows because of something called chrono selection. The drugs kill the sensitive cells, but they don’t kill the bad cells, and that’s how we can get all of those changes and mutations.

Katherine Banwell:

Okay. Dr. O’Donnell, is the process for choosing treatment different for a relapsed or refractory patient?

Dr. Irene Ghobrial:

So, that’s a great question. Yes, it can be. I mean, again, it always depends on how the person is doing at that time. It also depends, there are certain drugs that may not be approved in the front lines, something like venetoclax (Venclexta). If a person has a specific translocation, this 11;14, that’s something that we would like it in a second-line setting, for example.

Usually one of the big questions people ask is if you’re on a specific class of drugs, should you change classes? So, this example is if you’re on lenalidomide (Revlimid), and you have evidence that your disease is progressing, should you change to a different type of drug? A proteasome inhibitor, monoclonal antibody? Should that include one of the same classes of drug, like pomalidomide (Pomalyst), which is the next generation?

So, there are a lot of different factors that we consider. The number of drugs. So, you know, as Dr. Nadeem said, historically – there’s a lot of history in myeloma therapy, and it’s been an evolution, and so now we’ve had people who were treated with the three-drug combination that are starting, after many years, to progress. So, we might choose a monoclonal antibody for those patients because it wasn’t available at the time they were diagnosed. Versus patients now, who are typically on a four-drug regimen that includes those monoclonal antibodies and all the different classes of drugs.

We’re looking at different and, if available, novel agents to put those patients on. And again, I think Dr. Nadeem made a really important point that I want to underscore, which is that very often our best therapies are available in clinical trials. And so when and if there is the opportunity to be on a clinical trial, you may be then able to get something that would not otherwise be available to you. So, I encourage people to always have an open mind to being on a clinical trial at any stage in their disease treatment.

Katherine Banwell:

What therapies are available for relapse or refractory disease? Are they different than other therapies?

Dr. Betsy O’Donnell:

You know, so that’s a great question. So, yes and no. I highlighted one example that might be a little bit different, but in general, we’re very fortunate that we have multiple classes of drugs, meaning we have different drugs that work differently to kill your myeloma cells. And as Dr. Nadeem said earlier, we use those in combinations to increase the effectiveness of those medicines. Within each class we have a variety of drugs.

You used the example of immunomodulators, and show that we have three different of those type of drugs.

We have two different proteasome inhibitors. Beyond that, we have other classes of drugs that were mentioned. We have monoclonal antibodies, immunotherapies.

And so very often we make, it’s almost like a mix where we pick what we think is going to be most effective, sometimes based on cytogenetics. The biology. Sometimes based on patient selection. What are their other medical problems, what are their current issues? And we pick the combination that we feel is going to be most effective from the different classes of drugs that we have together, usually trying to use multiple drugs in combination.

Katherine Banwell:

Well, what newer therapies are available or in development for refractory and relapsed disease?

Dr. Betsy O’Donnell:

So, I think that the greatest interest that I think we’re all most excited about is the immunotherapy space, and I think we’ve seen – for myeloma, we see that this is a relapsing and remitting disease.

And what’s been so exciting about CAR-T cells and the bispecific antibodies is that in patients who have had, on average, five relapses, we’re seeing tremendous results. So, complete remissions or very good partial remissions that last. In fact, can last up to two years, on average, with one of our CAR T-cell products.

So, this is really exciting, especially when you compare to what historically has been out there for patients who have had that many relapses. And just as Dr. Nadeem said, the way that drugs enter, they enter from the relapse refractory setting, ethically that’s what makes the most sense, and they march their way forward. And so that process is happening right now as we speak, and I think like Dr. Ghobrial talked about, is the importance in early disease of thinking about using these really exciting therapies in patients who have lower burdens of disease with a goal of cure.

And so I think all of us on this call are committed to one thing, and that is curing multiple myeloma, and even the precursors that lead up to it so that patients never have to go through the process of years and years of therapy. And so I think we’re very excited about what immunotherapy might be able to offer as we move forward in myeloma treatment.

How Is Research Advancing Myeloma Treatment and Care?

December 12, 2022/in INSIST! Myeloma, MM Insist Treatment, MM Newly Diagnosed, MM Programs, MM Testing, MM Videos ND, MM Videos T, Multiple Myeloma /by Kara Rayburn

How Is Research Advancing Myeloma Treatment and Care? from Patient Empowerment Network on Vimeo.

A panel of myeloma experts, including Drs. Omar Nadeem, Irene Ghobrial, and Betsy O’Donnell, discuss how clinical trials advance myeloma research and share an update on promising therapies in development.

Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.

Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Learn more about Dr. Ghobrial.

Dr. Betsy O’Donnell is Assistant Professor of Medicine at the Dana-Farber Cancer Institute specializing in Plasma Cell Disorders.

Understanding Personalized Medicine for Myeloma

Related Programs:

What Are Currently Available Myeloma Treatments?

Which Myeloma Patients Are Candidates for CAR-T Cell Therapy?

Transcript:

Katherine Banwell:

Where do clinical trials fit into a patient’s treatment plan?

Dr. Omar Nadeem:

Yes. So, clinical trials as a term, a lot of times patients have a lot of questions about what that means. There’s a lot of misconceptions, I would say.

Sometimes patients think they will get either a placebo and they won’t get the adequate treatment, or that they may not get the right treatment, right, because they’re taking a chance going on a clinical trial. It’s actually the opposite. So, all the trials are really designed to improve upon what we already know works in a particular disease, right? So, when we think about trials let’s say in relapsed myeloma, where the patient has already had some of the approved therapies, we’re looking at the most promising new therapies that have shown efficacy either in the lab or first in human studies and then moving them through the different phases and studying them in more and more patients.

And that’s how all these drugs get started, right? So, they all get started at that point and then make their way to earlier lines of therapy.

Then you’re trying to answer different questions as part of clinical trials. So, which one of these therapies can I combine, for example. Which ones can I omit, which ones – so, they’re all sort of getting the standard therapy and getting something either added on top of it or removed, depending on what the question that we’re asking.

And then in the world that we currently live in with precursor plasma cell disorders, as Dr. Ghobrial mentioned, we have lots of patients that are at high risk of developing multiple myeloma in their lifetime, and that could be in a few years to a decade. And a lot of these therapies are so effective, and we’re now trying to really study some of these rationally in that patient population, so that’s a very different clinical trial, for example, than what I described earlier.

So, it really depends on what you’re trying to achieve and where you are in the phase of your disease.

Katherine Banwell:

This next question is open to all of you. Are there therapies in development that are showing promise for patients with myeloma? Dr. O’Donnell, let’s start with you.

Dr. Betsy O’Donnell:

Yes. So, I think we are so fortunate in multiple myeloma to have so much interest in our disease and so many great drugs developed. So, as Dr. Nadeem was discussing, CAR-T cells are an immunotherapy, the ones that are approved now, we actually are fortunate to have two CAR-T cells approved, target something very specific called B-cell maturation antigen.

We’re now seeing the next generation where we’re looking at other targets on the same cancer cell, that plasma cell, so those are evolving.

Same thing is true in the bispecific antibody space. Again, those target BCMA now, but we have newer bispecifics who look at alternate targets, and really what this does is it gives us different ways of approaching the cancer cell, particularly as you relapse through disease.

Dr. Irene Ghobrial:

I would probably say we’re also getting into targeted therapies and more of personalized, so if you have an 11;14 translocation, venetoclax (Venclexta) would be an amazing drug for that. And the more we can say my own personal myeloma, what’s the best treatment for me, that’s how we’re trying to do it. So, it may not be exactly precision medicine, but we’re getting closer and closer to precision medicine of my myeloma, my specific drugs. And even if people have a 17p deletion, then we would say let’s think of that immunotherapy.

It is truly a renaissance for us, and we’re starting to get into trispecifics, into off-the-shelf CAR-T, into so many new things. Into two different antigens that are expressed for the CAR-Ts. I mean, we are really beginning the era of immunotherapy, and we’re excited to see how much we can go into that because it will completely change myeloma, and hopefully we will cure many patients. We think we have already amazing drugs. It’s a matter of when to use them and who is the right person for this right drug.

Katherine:

What are you hopeful about the future of care for myeloma patients? Dr. Ghobrial, do you want to start?

Dr. Irene Ghobrial:

I’m hopeful that we truly cure myeloma, and no one should ever develop end organ damage.

We should identify it early and treat it early, and no one should ever come in being diagnosed with multiple myeloma.

Katherine Banwell:

Okay. Dr. Nadeem?

Dr. Omar Nadeem:

Yes, I think I definitely agree with what Irene said, and really having a more thoughtful approach to each individual myeloma patient. As I mentioned earlier, we have so many available therapies. I want to be able to know exactly which patients need which path in terms of treatment, and which ones we can maybe de-escalate therapy, right? So, thinking about which patients do well and maybe can get away with not being on continuous therapy, and those that absolutely need it. Identifying them better to give them the best therapy.

Katherine Banwell:

Dr. O’Donnell, do you have anything to add?

Dr. Betsy O’Donnell:

I think we all share a common goal, which is cure, and for those who we can’t cure yet, I think really working on making the experience as good as it possibly can be and focusing on the factors that we can control and optimizing those, both for patients and their caregivers who are in this journey together with the patient.

What Should Patients Know About Myeloma Testing?

December 12, 2022/in INSIST! Myeloma, MM Insist Testing, MM Newly Diagnosed, MM Programs, MM Testing, MM Videos ND, MM Videos T, Multiple Myeloma /by Kara Rayburn

What Should Patients Know About Myeloma Testing? from Patient Empowerment Network on Vimeo.

Testing following a myeloma diagnosis, or relapse, can impact care and treatment decisions. Drs. Betsy O’Donnell and Omar Nadeem provide an overview of essential myeloma testing, how the test results impact staging, and discuss recent advances in testing that have changed myeloma care.

Dr. Betsy O’Donnell is Assistant Professor of Medicine at the Dana-Farber Cancer Institute specializing in Plasma Cell Disorders.

Understanding Personalized Medicine for Myeloma

Related Programs:

How Is Research Advancing Myeloma Treatment and Care?

How Is Myeloma Treatment Response Measured?

Transcript:

Katherine Banwell:

Dr. O’Donnell, let’s move on to testing. What tests are necessary to help understand a patient’s specific disease?

Dr. Betsy O’Donnell:

Absolutely. So, testing really does depend a little bit on the stage at which your disease is found. In general, we use a very specific blood test that lets us know that there is clonal protein present. Remember, plasma cells are a type of white blood cell, and they make something called antibodies. We use a test called a serum protein electrophoresis, which is a blood test – an SPEP, we call it – that can tell us the difference between normal, healthy antibody and clone that are made from the plasma cells that we see in MGUS, smoldering, and multiple myeloma.

So, that’s a very important test, and sometimes your primary care doctor may notice that your total protein is elevated and send that test.

Or there may be other things that tip them off. Perhaps the kidneys are not where they used to be. And so that test is sent, and that’s the first tip-off that someone might have a plasma cell disorder.

Once we identify that there’s a plasma cell disorder, then that can set in place a workup, depending on the amount of clonal, monoclonal, M-protein that we see. So, sometimes that involves bone imaging. Historically that was a skeletal survey where we took lots of X-rays of your body. Now we have other tests we use. PET scans, CT scans, whole body MRIs. Sometimes it depends where you’re getting your treatment, and also it depends a little bit on your doctor’s degree of suspicion.

Bone marrow biopsies are a procedure that we sometimes do. We use a thin, hollow needle to take out just a little piece of bone, about the size of an inchworm, and take some fluid with it. There’s actually fluid inside the bone marrow.

And that can tell us, just as Dr. Ghobrial was defining the spectrum of plasma cell disorders, based on the percent of plasma cells, that can tell us where somebody belongs, which group they might belong in. So, we can use all of these tests to help give us a good sense of how much disease someone has and where in the spectrum or continuum a person is – MGUS, smoldering, or multiple myeloma.

Katherine Banwell:

Okay, great. Thank you. I’m assuming these tests can help with understanding the stage of a patient’s myeloma. So, Dr. Nadeem, how is myeloma staged?

Dr. Omar Nadeem:

Yes. So, myeloma is staged very differently than traditional cancers. Because this is a blood disease, we don’t really think about it like we may in other solid tumor cancers, where if it’s spread to multiple locations it’s IV, etcetera. That doesn’t apply to multiple myeloma. It’s actually staged out of three stages, and uses your blood work for the most part, some blood tests, to help identify which stage you are. Historically, that has correlated with how you may do.

However, now we are learning that it’s far more to this story than just the blood work. So, we’re now using our bone marrow test results, particularly a test called a FISH test, which looks at the mutations that are present in examinable plasma cells, and if you have presence of some of these high-risk markers, that can actually either upstage you or downstage you if you don’t.

So, we’re now I think becoming a little bit smarter how we think about this disease. It’s not just based on some blood test. We’re actually looking at the biology of some of these cells and the amount in the bone marrow. A lot of times patients ask, “Well, if I have 50 percent, 60 percent, or 80 percent involvement of the bone marrow, that actually does not have anything to do with staging, right?” So, I think it’s important to know that it’s actually a very unique staging system in multiple myeloma.

Katherine Banwell:

Okay. Dr. O’Donnell, the landscape of myeloma has changed significantly in recent years. How have advances in testing changed care from myeloma patients?

Dr. Betsy O’Donnell:

So, I mean, the landscape has changed incredibly just in terms of the treatments we have, and I think that Dr. Nadeem was talking about something really important.

In that when we look at FISH, which allows us to know the biology a little bit more, sometimes it helps us to decide kind of the risk that a patient is. We aren’t really at the point now where we do truly tailored therapies, like you see in some cancers, where we can detect specific mutations and pick drugs that align with that, but there are some that we do use. An example would be a drug called venetoclax (Venclexta), which works very well in patients who have a specific translocation, 11;14.

So, there is some degree in which we use that FISH and those cytogenetics to help define our treatments, but also really we’re just fortunate that we have new and evolving therapies. We’ve changed how we treat myeloma in the up-front setting, and then at the back end we have an exploding field of immunotherapies, CAR-T cells, bispecific antibody that we’re now using that really have tremendously benefited our patients.

Katherine Banwell:

Dr. O’Donnell, should all patients undergo in-depth testing, like cytogenetics?

Dr. Betsy O’Donnell:

Yes, so if you’re doing a bone marrow biopsy, absolutely. The question in terms of who needs bone marrow biopsies, if someone has a low risk MGUS, those patients don’t necessarily require a bone marrow biopsy. It’s an invasive procedure, it’s an uncomfortable procedure. But if we’re doing a workup for multiple myeloma or smoldering myeloma that includes a bone marrow biopsy, then absolutely.

Katherine Banwell:

Okay. Dr. Nadeem, what are you looking for with cytogenetics, and how might test results affect prognosis and treatment?

Dr. Omar Nadeem:

Yes, so as mentioned earlier, there are some mutations that are considered high risk, I will say with the caveat that we don’t fully understand every single mutation yet or have identified every single mutation yet that may be high risk or low risk.

But there are roughly five that we have identified that if a patient has one or two or several of those abnormalities, then their disease may behave a little bit more aggressively or may not respond as well to treatment.

However, I think myeloma is just very complicated, so we look at a lot of these results in the beginning, both whether they may be good or bad. But I think, ultimately, we have to see how patients do, and that by far is the most important prognostic factor, in my opinion. So, if we look at some of these tools, including staging, some of the bone marrow results and cytogenetics, and try to give some prediction in terms of what we may see from this person’s disease, but ultimately the treatments that are so effective now really dictate the course for the majority of the patients.

Katherine Banwell:

Are there specific tests that patients should ask for that could impact their care decisions?

Dr. Omar Nadeem:

Yes, I think it depends on where they are in their disease state. So, if we’re looking at whether a patient has a precursor or plasma cell disorder or multiple myeloma, then they need all the testing to help us figure that out.

So, that includes a bone marrow biopsy, the FISH testing as we just talked about. Advanced imaging like a PET scan or an MRI is now critical to identify patients that may have multiple myeloma versus those that have a precursor condition. So, we used to count on X-rays, as Dr. O’Donnell mentioned, but now really we do prefer one of those advanced imaging techniques for patients to undergo so that we can know.

So, I think if they have basically those tests completed, that gives us most of the information that we need.

How Does Disease Staging Affect Myeloma Treatment Choices?

October 31, 2022/in Engaging in Myeloma Treatment Decisions, MM Newly Diagnosed, MM Programs, MM Videos ND, Multiple Myeloma, Treatment Options /by Kara Rayburn

How Does Disease Staging Affect Myeloma Treatment Choices? from Patient Empowerment Network on Vimeo.

What are the stages of myeloma, and how does this affect care? Dr. Abdullah Khan, a myeloma specialist, reviews how myeloma is staged, which genetic markers may affect risk, and the impact of staging on treatment decisions.

Dr. Abdullah Khan is a hematologist specializing in multiple myeloma and plasma cell disorders at the Ohio State University Comprehensive Cancer Center – The James. Dr. Khan is also an assistant professor in the Division of Hematology at The Ohio State University. Learn more about Dr. Khan.

Related Resources:

Expert Advice for Newly Diagnosed Myeloma Patients

Myeloma Induction and Consolidation Therapy Defined

$Relapsed and Refractory Myeloma Defined$

Relapsed and Refractory Myeloma Defined

Transcript:

Katherine:

How does staging affect treatment option?

Dr. Khan:

Staging is done by two methods. The older method is the international staging system, abbreviated as ISS. And then there’s the newer revised ISS, or RISS.

The patients are assigned stages one to three. To determine the ISS you need lab values for the beta-2 microglobulin and albumin. For the revised ISS, you add on the lab value for LDH, lactate dehydrogenase, and you also add in the chromosome risk profile. So, there are certain genetic changes that predict a more aggressive myeloma. And the ones added to the revised ISS staging system are translocation 4;14, translocation 14;16, and deletion 17p.

So, that’s the ISS stage and the revised ISS stage. There are also other factors patient providers look into when determining the risk profile for patients. So, that might include other genetic changes.

One that is gaining a bit more traction right now is something called gain 1q, or amplification 1q, so more than one copy of part a chromosome. Some patients might have myeloma that doesn’t start, and the bone marrow might be found outside of the bones. And that’s called extramedullary disease, and sometimes that’s kind of high-risk. And some people have so much bone marrow plasma cells that it actually spills into their bloodstream. So, they might have high circulating plasma cells. Anyway, this will give information on staging.

And in terms of how it affects treatment option, I’ll give maybe two examples. Let’s say in case one we have a 40-year-old patient high-risk multiple myeloma. The high risk portends a poorer prognosis, meaning the outcomes might not be as good as someone with a standard myeloma. So, in that case, I might try to do or use the most aggressive treatment option in order to maximize treatment responses because I know the overall outcome is poor.

I do all this while acknowledging maybe the chances of having side effects might be higher, but that might be an acceptable tradeoff.

In case two, I’ll flip to an 80-year-old with standard risk cytogenetics.

So, I predict their myeloma to behave standard. In this case, I might try to use a regimen with a more acceptable safety profile, because the predicted response to treatment is anyways very good. So, I don’t want to hurt them in the process of getting their myeloma in remission.

I’ll also say this. My practice pattern at The Ohio State University might be a little different than someone on the East Coast or West Coast, and that’s okay. We all have our experiences with the different treatment regimens, but we all have the same goal of being as aggressive as we can while being mindful of side effects.

Advances in Myeloma Molecular Testing

October 31, 2022/in INSIST! Myeloma, MM Insist Testing, MM Newly Diagnosed, MM Programs, MM Testing, MM Videos ND, MM Videos T, Multiple Myeloma /by Kara Rayburn

Advances in Myeloma Molecular Testing from Patient Empowerment Network on Vimeo.

What is molecular testing, and how does it impact myeloma care? Dr. Abdullah Khan from the Ohio State University Comprehensive Cancer Center – The James discusses the specific markers found in cytogenetic analysis that determine a patient’s risk and may impact treatment choices.

What Tests Are Essential Before Choosing a Myeloma Treatment Approach?

Related Programs:

Understanding MRD and What It Means for Myeloma Patients

How Do Test Results Impact Myeloma Treatment Options?

Transcript:

Katherine:

Have there been advances in molecular testing for myeloma patients?

Dr. Khan:

Molecular testing is a broad term and can indicate checking genes, proteins, and other molecules. Even let’s say speaking outside of the world of myeloma, molecular testing can be used to determine in individuals if they have a high chance of developing cancers or other diseases.

It can be done to confirm so cancer diagnoses using the tissue biopsy specimens. It can also be used to help plan treatment, find out how well the treatment is working, provide prognosis information, and other information. In the world of myeloma, there are – in the world of myeloma, there are researchers looking at all of these molecular changes that can happen with disease.

Katherine:

So, how do the results of these tests affect treatment?

Dr. Khan:

There’s a particular cytogenetic change called translocation 11;14 that’s found in maybe a quarter of all patients with newly diagnosed myeloma, and it predicts a high likelihood of responding to a new drug called venetoclax.

In the clinical trial of venetoclax, when it was given to all patients with multiple myeloma, there was actually higher mortality in patients when given venetoclax in combination with bortezomib and dexamethasone. And this is despite a higher response rate by adding the venetoclax.

The thought process was maybe those patients were not doing well because of higher chances of serious infections. But when they took the data and they looked at that subgroup of patients with the translocation 11;14, there was no such concern in that subgroup. So, in this case of having translocation 11;14, it actually giving you a new treatment option based on the findings of the molecular testing.

We participate in a national clinical trial called MyDRUG, and that’s looking at other molecular changes to see if a more targeted treatment when added to the backbone of myeloma therapies translates to better outcomes.

Another recent development in molecular testing is diagnostic testing for minimal residual disease, and that’s from the bone marrow in patients with multiple myeloma.

The most commonly used test in clinical trials is the clonoSEQ test; it’s an FDA-cleared diagnostic test. The way it works it looks for specific DNA sequences on the receptors of the cancer cells. So, each cancer cell has like a genetic barcode.

Using the liquid part of the marrow, we can look for those cells that harbor that genetic barcode.

And the test is so sensitive, we can find one in a million cells in a patient’s bone marrow aspirate. So, it’s a very sensitive test, but it is not yet approved for making treatment decisions. One way we can use it though is for prognostic information. So, a patient attaining minimal residual disease-negative status or MRD-negativity, probably will do better than someone who has MRD-positive disease.

And there’s an emerging concept called sustained MRD negativity. So, let’s take an example of someone getting MRD testing at one year and two years after their stem cell transplant. The patient who is MRD-negative at both the one-year and two-year marks will likely do better than the one who is MRD-negative at one year but turns positive at the two-year mark.

So, these are some of the new developments in molecular testing in multiple myeloma.

How Often Do CLL Patients Develop a Second Gene Mutation?

May 11, 2022/in Chronic Lymphocytic Leukemia, CLL Newly Diagnosed, CLL Programs, CLL Start Here, CLL Start Here Q&A, CLL Testing, CLL Treatments and Clinical Trials, CLL Videos ND, CLL Videos T, CLL Videos TC /by Kara Rayburn

How Often Do CLL Patients Develop a Second Gene Mutation? from Patient Empowerment Network on Vimeo.

Chronic lymphocytic leukemia (CLL) patients can sometimes develop a second gene mutation. Watch as Dr. Nadia Khan from Fox Chase Cancer Center shares how common it is to develop a second mutation and when it’s important to retest for genetic changes.

See More from START HERE CLL

Related Programs:

Are There Any Long-Term Side Effect Risks for CLL Patients?

What Tests Should I Get Before Seeing a CLL Specialist?

How to Approach Side Effects with CLL Medications

Transcript:

Mary Leer:

This question comes from Laurie. How common is it for CLL patients to develop a second gene mutation?

Dr. Nadia Khan:

Laurie, Thanks for that question. It is not common for most call patients to have significant alterations in the genetic landscape of the CLL. With that being said, there are a few notable exceptions for CLL with TP53 dysfunction or complex cytogenetics, there is a higher likelihood that there will be genetic instability in those CLL clones. Therefore, it’s important to retest for changes if there is a change in the biology of the CLL, if there is a progression on therapy, for example, or at the time when a new therapy is planned.

How Is Myeloma Treatment Effectiveness Monitored?

December 6, 2021/in INSIST! Myeloma, MM Insist Testing, MM Newly Diagnosed, MM Programs, MM Testing, MM Videos ND, MM Videos T, Multiple Myeloma /by Kara Rayburn

How Is Myeloma Treatment Effectiveness Monitored? from Patient Empowerment Network on Vimeo.

Once you begin myeloma therapy, how do you know if it’s working? Dr. Saad Usmani, a myeloma expert, shares how patients are monitored via various tests and reviews how minimal residual disease (MRD) testing plays a role in myeloma care.

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.

Which Tests Are Essential to Diagnose and Treat Myeloma?

Related Programs:

Questions to Ask Your Doctor About Essential Myeloma Testing

Transcript:

Katherine Banwell:

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 Banwell:

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

What Do Myeloma Test Results Reveal About Prognosis and Treatment?

December 6, 2021/in INSIST! Myeloma, MM Insist Treatment, MM Newly Diagnosed, MM Programs, MM Testing, MM Videos ND, MM Videos T, Multiple Myeloma /by Kara Rayburn

What Do Myeloma Test Results Reveal About Prognosis and Treatment? from Patient Empowerment Network on Vimeo.

Myeloma expert, Dr. Saad Usmani, discusses how risk stratification is used in the care and treatment of patients with myeloma. Dr. Usmani reviews important test results that are used to classify low- and high-risk myeloma and the impact on treatment choices.

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.

Understanding Your Role in Myeloma Treatment Decisions

Related Programs:

How Does Essential Testing Affect Myeloma Care and Treatment?

Transcript:

Katherine Banwell:

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 Banwell:

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 Banwell:

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 autologous 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 Banwell:

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 RVD or carfilzomib 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 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.

Which Tests Are Essential to Diagnose and Treat Myeloma?

December 6, 2021/in INSIST! Myeloma, MM Insist Testing, MM Newly Diagnosed, MM Programs, MM Testing, MM Videos ND, MM Videos T, Multiple Myeloma /by Kara Rayburn

Which Tests Are Essential to Diagnose and Treat Myeloma? from Patient Empowerment Network on Vimeo.

Several tests follow a myeloma diagnosis and continue throughout one’s care. Myeloma expert Dr. Saad Usmani provides an overview of these essential tests, including blood tests and cytogenetics, and how the results impact overall treatment options.

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.

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

Related Programs:

What Should You Ask Your Doctor About Myeloma Testing?

Transcript:

Katherine Banwell:

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 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 Banwell:

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 3. If they don’t have them, they’re stage 1. If they have some of the features, they’re kind of in between in stage 2. And that’s how we stage multiple myeloma.

Katherine Banwell:

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 Banwell:

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

Dr. Usmani:

Yes.

Katherine Banwell:

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.

How Does Essential Testing Affect Myeloma Care and Treatment?

December 2, 2021/in INSIST! Myeloma, MM Insist Testing, MM Newly Diagnosed, MM Programs, MM Testing, MM Videos ND, MM Videos T, Multiple Myeloma /by Kara Rayburn

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.

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

Related Programs: