venclexta Archives

How Can CLL HCPs Gain More Understanding of Mutation Profiles?

Related Resources:

CLL Expert Updates on Diagnostic Tool and Technology Advances

CLL Clinical Trials for Molecularly Defined Patient Subgroups

Transcript:

Dr. Nicole Rochester:

Along with therapies, of course, come potential side effects. Are there any strategies that you can share with our healthcare provider audience around innovative approaches or protocols that have been implemented to mitigate and manage the CLL side effects from the treatment?

Dr. Callie Coombs:

I think it comes down to your internal resources, but I would say taking care of CLL patients is clearly a team effort. And so it’s not just me, but also a team of additional practitioners that I work with. So I’d like to emphasize how important pharmacists are because I’ve definitely seen some side effects that come about because a patient is now on a medication that interacts with whatever their CLL therapy is, which drives up the levels of the drug and then brings out certain toxicities so they can help us identify these if, perhaps I missed it or didn’t ask the patient about a supplement, et cetera.

Next is nurse practitioners and oncology nurses. And so number one is it’s a team-based approach, and I think it’s certainly very important to have protocols internally. But also to just realize what the common toxicities are and how can we mitigate these.

One of the most common reasons that I’ve seen for patients stopping a drug prematurely actually is venetoclax (Venclexta). It very commonly causes neutropenia. And I’ve seen the drug given up on very early without any growth factor support, and so I think if you become educated and experienced with using drugs, you can realize there’s very clear strategies in improving patients with neutropenia, by supporting them with growth factor and getting them through whatever their defined plan course of venetoclax may be.

And then BTK inhibitors have a whole smattering of side effects as well where perhaps working with cardio oncologists can help in addition to other strategies depending on exactly what side effect the patient may encounter. So in summary, definitely a team-based effort and growing experience with the common side effects helps I think all comers with strategies to help prevent or mitigate such side effects.

Dr. Nicole Rochester:

Thank you so much, Dr. Coombs. Dr. Brown, do you have some additional best practices you’d like to share with regard to the management of treatment side effects?

Dr. Jennifer Brown:

Well, I agree completely with Dr. Coombs. I would just add that I think it helps a lot when you warn the patients ahead of time about things that may happen but that often go away or that you can manage. So, for example, headaches often happen early on when you initiate acalabrutinib (Calquence) but they go away typically very quickly. And so if patients know that, then they’re much less worried, and then you can talk to them about the strategies, because caffeine or acetaminophen (Tylenol) will often help with that. If you warn them that they may have some joint aches or pains, that can also help, since those are often transient.

With venetoclax, warning them about some nausea or diarrhea, and then we often manage that by subsequently moving the drug to the evening after they’re done with their ramp up, or initiating an antiemetic, things like this. And then oftentimes many patients who have that in the beginning, it doesn’t persist throughout the whole time that they’re on the drug. Sometimes the diarrhea may, but many times it doesn’t. So getting the patients through that early phase with the close management, which again, it helps, have your team help with that, the nurse practitioners, et cetera, and then hopefully things settle out and everyone’s happy.

Dr. Nicole Rochester:

Wonderful. I just want to emphasize two things. One that each of you said. One is this idea of a team-based approach, which is important in the treatment of all diseases, but of course very important in the treatment of the cancer. And also this idea of educating our patients so that they know ahead of time what to expect and really involving them as part of the team. So I really appreciate those, both of those points.

Share Your Feedback

CLL Clinical Trials for Molecularly Defined Patient Subgroups

July 17, 2024/in EPEP, EPEP CLL, EPEP CLL Roundtable /by Kara Rayburn

CLL Clinical Trials for Molecularly Defined Patient Subgroups from Patient Empowerment Network on Vimeo.

What’s the latest in chronic lymphocytic leukemia (CLL) clinical trials for molecularly defined patient subgroups? Experts Dr. Jennifer Brown from Dana-Farber Cancer Institute and Dr. Callie Coombs from the University of California, Irvine discuss research updates for CLL patient subgroups, resistance mutations, and drug intolerance.

Download Resource Guide | Descargar guía de recursos

How Can CLL HCPs Gain More Understanding of Mutation Profiles?

Related Resources:

CLL Expert Updates on Diagnostic Tool and Technology Advances

Managing CLL Side Effects | Innovative Strategies and Approaches

Transcript:

Dr. Nicole Rochester:

So now we’re going to shift to talking about clinical trials and novel targets focused on molecularly defined patient subgroups. We know that by understanding the molecular profile of a patient’s CLL, that oncologists can choose the most effective therapies. So, Dr. Brown, I’m going to start with you for this one. Can you talk about any emerging CLL trials targeting specific molecular subgroups, and also how can CLL experts stay updated on these advancements in clinical trials?

Dr. Jennifer Brown:

So, as you heard from Dr. Coombs, there’s increasing interest in looking at high-risk patients in particular, and I think looking specifically at patients with p53 aberration in dedicated clinical trials, it’s become increasingly clear that the behavior of the disease when it’s higher risk based on p53 mutation, NOTCH mutation, IGHV status is quite different, particularly with time limited therapy compared to lower risk disease. And so having dedicated trials that evaluate outcomes specifically in certain of these subgroups is increasingly important. We do have more trials than we used to focusing specifically on p53 aberration.

My personal belief is that we would be well served to have trials separately in the IGHV groups that Dr. Coombs mentioned, although that has not gained as much traction. And then what we are seeing is now that there are resistance mutations, it actually has turned out that some of the drugs that we use in that setting, venetoclax (Venclexa) and pirtobrutinib (Jaypirca), seem to have pretty similar activity in patients with and without the mutations. But as drugs are being studied in this context, there’s been an increasing tendency to study them in specific subgroups.

So patients who have the mutation and had clinical progression on a covalent inhibitor, patients who don’t have the mutation and had clinical progression, patients who may have come off their covalent inhibitor for adverse events who may not actually be resistant, what is their response to the next line of therapy? And so all of that is just helping us understand in a more nuanced way what the best benefit for patients will be as we look at these different subgroups of patients.

Dr. Nicole Rochester:

Thank you, Dr. Brown. Appreciate that. Dr. Coombs, do you have anything to add?

Dr. Callie Coombs:

Yeah, so I echo all of Dr. Brown’s comments, and I think I’m the person that is bringing all the practical aspects of CLL care because it’s, she’s so thorough. I just always like to contribute a few little pearls. So, pirtobrutinib has been an exciting drug, to see it become available for our double refractory patients. So the current FDA indication is for patients failed by not only a covalent BTKi but also venetoclax. But it’s the first BTK inhibitor that we can effectively use in the setting of a prior BTK inhibitor.

And that’s because of this unique aspect where instead of forming a covalent bond at the C481 residue, it binds reversibly, and we can still see activity. But the practical aspect is that that’s not an effective strategy when you have a patient progressing on, say, ibrutinib (Imbruvica), you can’t switch them to acalabrutinib (Calquence) or zanubrutinib (Brukinsa) because of their shared mechanism of resistance. They’re all covalent inhibitors. They all share the same mechanism of resistance.

And so that’s one thing I’d like to bring up. However, there’s a very different and very common clinical situation that I encounter really a lot in my clinic, which is intolerance. And so that’s where it would be a very effective strategy to switch a patient from one covalent drug to another. And so literally in the past couple weeks of clinic, I’ve had patients with chronic long-standing toxicities to ibrutinib (Imbruvica) that perhaps went underrecognized where I say, “Hey, you’ve had…notice your blood pressure has gone up a lot.

Let’s switch you over to acalabrutinib,” or other patients, “Oh, you’ve had issues with atrial fibrillation, it…let’s try switching you to zanubrutinib.” Because the rates are a lot lower and a lot of patients can have improvement or just complete resolution of the prior side effect. And so I hope that that emphasizes this is something that we think about every day, and switching is appropriate in the setting of intolerance. It’s not appropriate when you’re staying in the covalent class to switch in the setting of progression. But pirtobrutinib being a non-covalent inhibitor is certainly very effective after a covalent. And I think once we see readout of some of the ongoing Phase III trials, we may be able to use it in that setting under an approved FDA label, though that is to be seen in the future.

Share Your Feedback

CLL Expert Updates on Diagnostic Tool and Technology Advances

July 17, 2024/in EPEP, EPEP CLL, EPEP CLL Roundtable /by Kara Rayburn

CLL Expert Updates on Diagnostic Tool and Technology Advances from Patient Empowerment Network on Vimeo.

What diagnostic tool and technology advances for chronic lymphocytic leukemia (CLL) are available in clinic, and which ones are in the research setting? Experts Dr. Jennifer Brown from Dana-Farber Cancer Institute and Dr. Callie Coombs from the University of California, Irvine discuss next generation sequencing and research that is under study for CLL mutations.

Download Resource Guide | Descargar guía de recursos

How Can CLL HCPs Gain More Understanding of Mutation Profiles?

Related Resources:

CLL Clinical Trials for Molecularly Defined Patient Subgroups

CLL Expert Perspectives on Current and Future Patient Care

Transcript:

Dr. Callie Coombs:

I think an argument could be made in practice whether or not sending these mutation tests is beneficial, but research, clearly important, and I think it’s going to give us key insights into our therapeutic sequencing strategies going forward. So I’m certainly a proponent of doing the testing in a well-monitored setting, but I don’t think it’s ready for prime time to be applied completely broadly to our patients.

Dr. Nicole Rochester:

Thank you, Dr. Coombs, and I appreciate you adding that additional practical tips and information specifically for our healthcare providers. And you kind of moved into the next topic, which was really around new diagnostic tools and technologies that are available to detect and monitor mutations. So I’m going to go back to you, Dr. Brown, to see if you have any additional information that you’d like to share about new diagnostic tools, technologies with regard to these mutations and any other tips perhaps for our healthcare provider audience.

Dr. Jennifer Brown:

Well, and really the only issue is what Dr. Coombs mentioned that it’s very important to get a next generation sequencing test to evaluate the p53 mutation, that it really is not well-evaluated by any other test, and is often missed because it’s thought that checking for the deletion is sufficient. So I would just reemphasize that point that she made very clearly. Other than that, we don’t really need any additional tools to monitor for mutations.

In the research setting, we’re trying to do more and more sensitive assays to try and see when the earliest time that these mutations may emerge is and is there a way we could prevent that or, and just to better understand some of the biology, but it’s not really anything that’s needed in clinical practice. And we’re also not using the mutations to monitor residual disease. It turns out that the best way to do that is probably looking at the B-cell receptor itself, which is again, something that we’re studying in the research setting, but is not really something that needs to be done in clinical practices yet.

Dr. Nicole Rochester:

Wonderful. Thank you, Dr. Brown. We definitely want to leverage you all’s expertise in this area. And so my next question has to do with practices. And you’ve really kind of addressed this to some extent already. Are there any unforeseen or perhaps outdated practice-related barriers that may either hinder your work or that of your colleagues specifically related to better understanding CLL mutations?

Dr. Callie Coombs:

Yeah, I mean, I think in addition to what I mentioned about 17p and TP53, one type of mutation we haven’t talked about is assessing for the mutation status of IGHV. So that’s actually something else that I’ve seen frequently missed as far as the routine testing of a CLL patient. But I do think it’s very important to send. Is it as important as when we were in the chemoimmunotherapy era where it would be hugely predictive for who had a long remission and who wouldn’t?

Maybe not as important, but I do think if someone’s unmutated that still can really help inform certain aspects of their journey. One is the time that between diagnosis and when he or she’ll need their first treatment. But two, also the expected length of remission should this patient embark upon a time-limited regimen such as venetoclax (Venclexta) and obinutuzumab (Gazyva).

But the separate question is, again, coming down to the practical aspect of how IGVH is tested. So another misunderstanding that I’ve seen is FISH tests look for the IGH locus. And so I’ve seen on recurrent occasions if that’s deleted, they say, “Oh, that’s a mutation.” Well that’s definitely not the same thing, and so it’s just to realize the IGHV test is a very specific test.

Some large facilities do it as an in-house test, I myself have been sending mine out to the Mayo Clinic, there’s other vendors where you can do it, but what they do is they specifically sequence IGHV and then compare the patient sequence to a consensus germline sequence to determine the percent of mutation, and it’s actually a good thing to be mutated with this gene, these are the patients that often have a longer time until they need their first treatment, if they need treatment at all, and then they generally have better responses to therapy. Though with BTK inhibitors, that difference is often becoming quite slim given that they work in both groups of patients.

Share Your Feedback

How Can CLL HCPs Gain More Understanding of Mutation Profiles?

July 17, 2024/in EPEP, EPEP CLL, EPEP CLL Roundtable /by Kara Rayburn

How Can CLL HCPs Gain More Understanding of Mutation Profiles? from Patient Empowerment Network on Vimeo.

How might chronic lymphocytic leukemia (CLL) HCPs gain more understanding of mutation profiles? Experts Dr. Jennifer Brown from Dana-Farber Cancer Institute and Dr. Callie Coombs from the University of California, Irvine discuss several mutations, how they commonly impact treatment, and acquired resistance to inhibitors.

Download Resource Guide | Descargar guía de recursos

CLL Expert Updates on Diagnostic Tool and Technology Advances

Related Resources:

CLL Clinical Trials for Molecularly Defined Patient Subgroups

Managing CLL Side Effects | Innovative Strategies and Approaches

Transcript:

Dr. Nicole Rochester:

Dr. Brown, how do CLL healthcare providers better understand mutation profiles including the emergence of novel CLL mutations over time?

Dr. Jennifer Brown:

Well, the first thing that’s important to recognize is that CLL is not defined by any particular mutation. The landscape is quite varied and we see a large number of different mutations at low percentages. Well, the second key point to remember is that there are different mutations at baseline and then there can be acquired mutations that include some of what we see at baseline, but also novel resistance mutations that we don’t ever see at base.

So at baseline, the most common mutations, which are somewhere in the 10 to 20 percent range of patients, although less than that if you have very early stage patients, affect the p53 gene, NOTCH1, SF3B1, and ATM. P53 is the most important because that one does influence our thinking about the patients and our choice of therapy in some cases. P53 can be altered in CLL in two different ways. Actually, the most common way is as a deletion, deletion of the short arm of chromosome 17 or 17P deletion. About 75 to 80 percent of patients that have that deletion will have a point mutation usually in the other p53 allele. So they have double knockout of p53.

A small percentage of people with the deletion will not have the mutation. And then a certain number of patients will have just the mutation without the deletion. And one of the things that I’ve been very interested in for a while that we’re still trying to understand better is the implications of these different combinations of the way p53 can be affected in people with CLL, and that it may, in fact, be more adverse to have both alleles knocked out than single, although we don’t have great data for that as yet because most of the data that we have has combined all of it together.

But it’s very important to test for the p53 mutation alone because even if patients have only that one, at present, we consider the treatment implications of it all similarly regardless of how the p53 gene is affected. And then NOTCH1 is a fairly common mutation that always worries us a lot, because it’s associated with Richter’s transformation, which is a very high-risk event, but we don’t know anything to do about that to try and prevent it or to alter our therapy based on it.

So at the moment it’s mostly something that we are aware of that we keep an eye on but not that changes therapy. And SF3B1, ATM, and this long list of other genes that can be mutated in just a few percent of CLL, and mostly what we know about them is some biology that’s been studied, and then the fact that the more of these mutations are mutated in a patient that is associated with a worse prognosis, just a total number.

But that’s not something also that really alters our therapy. And then when patients go through lines of therapy, they can sometimes acquire mutations in these genes. So a patient can acquire a mutation in p53 or in NOTCH after their second or third line of therapy. But the mutations that are hottest right now, or that people are most interested in are some of the mutations that occur as resistance to therapy.

So in particular, that means BTK mutations. Covalent BTK inhibitors have transformed the therapy of CLL, and they bind to the cysteine 481 residue of BTK. So that means, as you might imagine, that if you mutate that cysteine so that the inhibitor can’t bind, that will be associated with resistance. And that, in fact, is what has been found that the cysteine to serine mutation at 481 is the most common resistance mutation in patients on covalent BTK inhibitors.

And in the case of ibrutinib (Imbruvica), it makes the inhibitor into a much weaker and non-covalent inhibitor. In the case of acalabrutinib (Calquence) and zanubrutinib (Brukinsa), it probably abrogates all activity. And so that’s a mutation that we will sometimes look for in patients with clinical progression on those drugs. There’s also a mutation in BCL2 that can occur in patients in venetoclax (Venclexta).

So another example of an on target resistance mutation. The role of that one is a little bit less clear, and testing for it is not as widely available, but we’re still working on that. Resistance to venetoclax is probably more complicated than resistance to BTK inhibitors, although there’s also a subset of patients who will get BTK inhibitors who have novel mechanisms of resistance not related to BTK that we don’t really know anything about as yet.

And then finally, the non-covalent BTK inhibitors are becoming available, pirtobrutinib (Jaypirca) was approved for CLL in the United States in December for patients who’ve had covalent BTK inhibitors and venetoclax. And we’re starting to see different mutations in BTK at different sites, even though pirtobrutinib has activity against the 481 mutation. So there’s going to be a lot of activity in this area in the next few years probably.

Dr. Nicole Rochester:

Thank you so much Dr. Brown, that was a very comprehensive overview of the mutations. Dr. Coombs, do you have anything that you want to add to what Dr. Brown said perhaps specifically around mutations associated with the progression of CLL?

Dr. Callie Coombs:

Sure. So, that’s a hard act to follow. She really took us through a whirlwind of everything mutation-related. I think what I would like to focus on in my answer is, well, what should we be testing for on a day-to-day basis in our CLL practices and what are some common misconceptions? So specific to TP53, I would say this is the most important test as far as all of the genetic tests that influences what we do day to day in the care of patients with CLL.

I test for this for my newly diagnosed patients who I think may be interested in enrolling in a clinical trial, first of all, so the standard of care in CLL is watch and wait, however, patients with higher risk disease may be eligible for trials looking at early intervention specifically the SWOG EVOLVE trial looking at early treatment. And so that’s one of the risk markers that can get a patient into the higher risk category of CLL where they could be eligible for a trial.

A common misconception I see is that 17p is the same thing as a TP53 mutation, it’s definitely not. So these are two different tests that have to be sent. 17p can be picked up on karyotype testing and on FISH testing where it looks for 17p deletion. However, mutations are a different test. And so I usually send a next gen sequencing assay that includes other genes.

However, you can test purely just for mutations in the TP53 gene, but again, that’s a sequencing test, so I’d like to convey that, somewhat a misunderstanding, but it’s such an important gene in CLL because when patients have TP53 aberrations, whether that’s 17P or a TP53 mutation or both, given that they can occur in isolation or together, these patients should never get chemotherapy, because they have extremely terrible responses to chemo, and that should not be part of the therapies offered to these patients.

The other interesting, I’d say controversial at least in 2024, is what is the role for mutation testing in the clinic in the setting of acquired resistance to inhibitors? So I think it’s very clearly important in the research setting where I think learning about the C481 mutation among others in the setting of covalent BTK inhibitors has shown us a lot about mechanism of resistance. But in the clinic, I don’t necessarily think that’s something that needs to be universally applied, given that it most of the time doesn’t affect what we would do clinically. And so one example is a patient comes in progressing on ibrutinib, maybe about two-thirds of them may have a mutation in the C481S. However, if they’re clinically progressing, they need to switch therapy.

Share Your Feedback

EPEP CLL Resource Guide en Español

June 26, 2024/in EPEP, EPEP CLL, EPEP CLL Resources /by Kara Rayburn

Descargar guía de recursos

EPEP CLL Spanish Guide

Download Resource Guide | Descargar guía de recursos

EPEP CLL Resource Guide

June 26, 2024/in EPEP, EPEP CLL, EPEP CLL Resources /by Kara Rayburn

Download Resource Guide | Descargar guía de recursos

EPEP CLL Resource Guide

What Are AML Inhibitor Therapies and How Do They Work?

June 14, 2024/in Acute Myeloid Leukemia, AML Elevate, AML Elevate Treatment, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

What Are AML Inhibitor Therapies and How Do They Work? from Patient Empowerment Network on Vimeo.

What are AML inhibitor therapies, and how do they work? Dr. Gail Roboz explains the different types of inhibitor therapies, their targets, the patient type they may benefit most, and a new class of targeted treatments.

Dr. Gail Roboz is director of the Clinical and Translational Leukemia Programs and professor of medicine at Weill Cornell Medicine and the New York Presbyterian Hospital. Learn more about Dr. Roboz.

See More from ELEVATE AML

Related Resources:

Choosing Therapy | How Are AML Treatment Goals Determined?

Expert Overview | AML Treatment Options and Phases of Therapy

What AML Patients Should Understand About Test Results

Transcript:

Katherine Banwell:

You mentioned one inhibitor as targeted therapy, but there are a couple of others. Would you briefly tell us about those?

Dr. Gail Roboz:

So, over the years recently, we have identified certain specific targets in AML which are resulting in the addition of medications on these standard backbones. So, the target for venetoclax (Venclexta) is something called BCL2, and actually, venetoclax probably makes all chemotherapy better. It’s kind of a controversial statement, but I’m going to stand by it. But in AML, it has been shown that the addition of venetoclax to lots of different backbones makes them work better. There are other things to hit, though.

For example, there are patients with AML who have something called a FLT3, F-L-T-3 mutation. This mutation also has specific inhibitors that are FDA-approved drugs that target specifically the FLT3 mutation, and if you have one of those, your doctor may add on a FLT3 inhibitor to either a lower intensity or an intensive backbone. Similarly, there are agents called IDH inhibitors. There are IDH1 and IDH2 inhibitors.

If I start getting into isocitrate dehydrogenase pathways on this webinar, I think everybody will click off, because it’s certainly bored all of the medical students in med school, and it’s pretty tough to understand. But the bottom line is it’s very cool stuff because that boring pathway in medical school that nobody really thought about too much is actually part of very, very, central cellular functions that are a vulnerability now that have been identified in leukemic cells that, if you hit them with these specific inhibitors, patients do better.

Now, couple of things for patients. It doesn’t mean that it’s better to have a FLT3 or an IDH mutation because the targeted therapies are available. So, a lot of patients are disappointed when they don’t have mutations. I don’t want you to think in that way. It’s not that it’s better, it’s different.

It identifies a different biology. If you have certain mutations, there are certain medications that may help you more.

That’s why I think the patients are learning quickly, too, to ask the doc – they may not remember the letters of the alphabet soup, but “Do I have something about my AML that can get one of these targeted therapies added on?” I think is a good question to think about. “Do I have something about my disease that has a specific drug that we’ve already learned makes outcomes better?”

Katherine Banwell:

There’s a new emerging therapy as well. Is it the menin inhibitor?

Dr. Gail Roboz:

I think that, in understanding different targets and different pathways, it leads me to a general statement that if you can get yourself potentially onto a clinical trial at an academic center, that is something to consider right out of the gate. Because there is a lot, a lot, a lot going on in this field right now.

What we are hoping, and the reason that I am talking to you about venetoclax and FLT3 inhibitors and IDH inhibitors, is because of all the patients who jumped onto those clinical trials and proved that those drugs are better. Some of them are my patients! I was fortunate on some of those early trials to have some real winners in patients who got onto the trials. They’re the ones who drove the success.

So, for example, menin inhibitors, which are very, very exciting, targeted agents for NPM1 and KMT2A mutations and rearrangements – these are complicated to remember as a patient, but there’s a cool drug out there that might be for you.

I think that patients who really think about asking the question wherever they are, the “Hey, I just got a diagnosis of AML. Is there a clinical trial that might look good for me?” I think is a great question to ask pretty much out of the gate.

Expert Overview | AML Treatment Options and Phases of Therapy

June 14, 2024/in Acute Myeloid Leukemia, AML Elevate, AML Elevate Treatment, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

Expert Overview | AML Treatment Options and Phases of Therapy from Patient Empowerment Network on Vimeo.

What are the treatment options and phases of therapy for AML? Dr. Gail Roboz discusses the various therapies available to treat AML and to maintain remission, the timing of these therapies, and novel treatment approaches offered.

Dr. Gail Roboz is director of the Clinical and Translational Leukemia Programs and professor of medicine at Weill Cornell Medicine and the New York Presbyterian Hospital. Learn more about Dr. Roboz.

See More from ELEVATE AML

Related Resources:

Choosing Therapy | How Are AML Treatment Goals Determined?

What Key Testing Occurs Following an AML Diagnosis?

What Are AML Inhibitor Therapies and How Do They Work?

Transcript:

Katherine Banwell:

Dr. Roboz, would you provide a brief explanation of the phases of therapy for AML?

Dr. Gail Roboz:

Yeah. So, here, too, I have to say that it’s more confusing than it used to be for the following reasons. So, historically and currently, we typically talk about induction as the first therapy that you’re going to get to get into remission.

Then, the treatment paradigm is you do something to get into remission; do some treatment to get into remission. After that, in the realm of post-remission therapy, there are different things that can happen. There can be something called consolidation, which might be another round of chemotherapy. Some patients get consolidation, some patients don’t. After consolidation, there can be a transplant.

So, you get into remission, you may or may not get a little bit of what’s called consolidation chemotherapy, and then go on to a transplant.

However, sometimes either after the transplant or after chemotherapy before ever getting or instead of ever getting a transplant, there might be ongoing treatment in a lower intensity ongoing basis that is called maintenance.

So, you’ve got to think about it as induction as what happens first, consolidation is something that happens when you’re in remission, and then maintenance usually refers to ongoing therapy that is different from consolidation.

It’s usually lower intensity, easier to take, oral types of treatment that may go on and on. And just to be incredibly confusing, it’s different from something like breast cancer, where often the patients are given, “You get six cycles of this, and then you’re done.” From AML, there’s actually often not that type of an obvious plan right out of the gate for the patient.

The answer will be, “It depends.” It depends. It depends how your treatment looks at this point in time. It depends how you look at this point in time.

So then, the patients say, “Well, aren’t you going to cure me of this? What are you doing? Aren’t you going to get rid of it?” So, historically, there are some patients who get cured with chemotherapy. They get chemotherapy to get into remission, they get some chemotherapy afterwards, and there’s a cure rate for some patients with that. The majority of patients who are cured with AML get an allotransplant, or a transplant from somebody else.

Then there’s a whole group of patients where we’re asking the question now, is it possible to get those patients beyond five years – so in oncology, five years is typically defined as cure. Can we get some patients with ongoing therapy to that past-five-year mark without a transplant? That’s in the zone of the ‘coming soon.’ Don’t have a ton of patients in that group right now, but hopefully we will.

Katherine Banwell:

You’ve mentioned some various treatment types that are used to treat AML. Can you share a brief overview of available treatments?

Dr. Gail Roboz:

So, the terminology that we use is a little bit annoying, because it is a little bit general. We say intensive and not intensive.

But historically, intensive chemotherapy referred to a combination of generally two types of agents, cytarabine (Cytosar-U) and an anthracycline, which is a class of chemotherapy, that either just those two together or in combination with sometimes a third or a fourth drug usually keeps people in the hospital for around a month. Not that the chemotherapy takes that long, but the treatment gets rid of basically a lot of cells in the bone marrow, good guys and bad guys, and it takes about three weeks for those normal cells to recover.

So, a standard intensive induction for AML is often around three to four weeks in the hospital, somewhere between three and five or so days of chemotherapy up front, depending on exactly what the protocol is. The classic regimen is actually still called 3+7, three days of one drug, seven of the other. But there are many variations of that that work.

The chemo is then stopped, the patient hangs out in the hospital, very frequently getting transfusions and antibiotics, and we wait for the bone marrow to recover.

Another current path that many patients are getting – almost all older patients, with ‘older’ being defined not by a specific age cutoff, but often 75 and older, almost everybody agrees no longer gets the classic chemotherapy that I just described. At some institutions, that 75 is going down, and even 70 and 65 and above are getting a new type of therapy, mostly because the new type of therapy is working pretty well. That is a combination of something called a hypomethylating agent.

Drugs like azacitidine (Vidaza, Onureg) or decitabine (Dacogen) in combination with a pill that has changed the landscape of AML more than any other called venetoclax (Venclexta). Venetoclax is a drug that is not exclusively used for AML.

It actually was originally approved for another type of leukemia. But I think that not many people would argue with the statement that what has changed absolutely the face of AML treatment has been this drug, because it’s a BCL2 inhibitor. What it does is it actually – cancer cells and leukemia cells in particular are very, very good at staying alive.

They don’t undergo cell death, they don’t want to die, and venetoclax brings down their forcefield so that those cells can actually undergo apoptosis and die.

Venetoclax in combination with azacitidine or decitabine has transformed the care of the disease, because many patients older than 65 – and the median age of diagnosis of AML is around 68 to 70. So, many patients never were well enough to have the intensive therapy. They weren’t going into remission, and they weren’t having prolonged survival often beyond a few months.

But now, those patients do actually much better with the combination of aza [azacitidine] and venetoclax. So typically, the induction path is going to be deciding who gets an intensive therapy backbone, usually associated with long hospitalization. Who gets a less intensive backbone – by the way, that is often associated with just the same hospitalization. So, that’s why I don’t love the term ‘low intensity,’ because that implies that it doesn’t work.

It does, and it also implies that you’re not going to be in the hospital. You probably will, because in the same way as for the more so-called intensive therapies, getting into remission involves getting rid of bone marrow cells and waiting for the normal ones to recover. Even if you are a patient who is getting the venetoclax combined with the azacitidine or decitabine, which is typically called low intensity, you may very well be in the hospital for a month.

Because depending on where you live and who your family is and how sick you might be, you will probably want us to watch you carefully during that first month, but it’s worth it. Because if you have a good chance of getting into remission, remission is what makes life better and life longer. So, we want to get patients into remission, even if it means upfront time in the hospital.

[ACT]IVATED AML Resource Guide III en español

May 29, 2024/in Acute Myeloid Leukemia, AML Activated, AML Activated Resource Guides, AML Newly Diagnosed, AML Programs, AML Resource ND /by Kara Rayburn

Descargar guía de recursos

Spanish_ ACTIVATED AML Resource Guide_Hantel

Descargar guía de recursos

[ACT]IVATED AML Resource Guide III

May 29, 2024/in Acute Myeloid Leukemia, AML Activated, AML Activated Resource Guides, AML Newly Diagnosed, AML Programs, AML Resource ND /by Kara Rayburn

ACTIVATED AML Resource Guide_Hantel

[ACT]IVATED AML Resource Guide II

April 22, 2024/in Acute Myeloid Leukemia, AML Activated, AML Activated Resource Guides, AML Newly Diagnosed, AML Programs, AML Resource ND /by Kara Rayburn

ACTIVATED AML Resource Guide_Taveras Alam

[ACT]IVATED AML Resource Guide II en español

April 22, 2024/in Acute Myeloid Leukemia, AML Activated, AML Activated Resource Guides, AML Newly Diagnosed, AML Programs, AML Resource ND /by Kara Rayburn

Spanish_ACTIVATED AML Resource Guide_Taveras Alam

Evolve Multiple Myeloma Resource Guide

April 22, 2024/in Evolve Myeloma, Evolve Myeloma Advocacy, MM Newly Diagnosed, MM Programs, MM Resources ND, MM Resources TC, MM Treatments and Clinical Trials, Multiple Myeloma /by Kara Rayburn

PEN-192_Evolve_ResourceGuideF