Dr. Manish Shah (Host): Welcome to Weill Cornell Medicine CancerCast, conversations about new developments in medicine, cancer care, and research. I'm your host, Dr. Manish Shah. And today, we'll be talking about some of the most interesting abstracts to be presented at the 2025 Annual Meeting of the American Society of Hematology, or ASH.

We have two fantastic guests today. Our first guest is Dr. Gail Roboz. Dr. Roboz is a Professor of Medicine and Director of the Clinical and Translational Leukemia Program at Weill Cornell Medicine/NewYork-Presbyterian Hospital. She has led numerous clinical trials, and her research focuses on developmental therapeutics for acute leukemia, myelodysplastic syndrome, and myeloproliferative disease.

Our second guest is Dr. Rick Furman. Dr. Furman is Director of the Chronic Lymphocytic Leukemia (CLL) Research Center at Weill Cornell Medicine and a member of the Lymphoma/Myeloma Service in the Division of Hematology and Medical Oncology. His area of focus is on the development of non-chemotherapeutic approaches to treating CLL. And he has played an integral role in the development of ibrutinib and idelalisib.

These are really two legends in the field of malignant hematology and it's an honor to have them here.

Gail and Rick, do you want to introduce yourselves?

Dr. Gail Roboz: Thanks so much for having me. I have been on the team at Weill Cornell and NewYork-Presbyterian Hospital for-- I don't even want to say how many years, but heading into 26 years as an attending, and then a resident and a fellow beforehand. So, I guess I am a lifer at this place.

Dr. Manish Shah: Thank you. And Rick?

Dr. Richard Furman: Manish, thanks for the invitation. It's great to be here. There's been so much change in how we treat our patients over the past 25 years. It's just great to have been a part of all of it and to talk about it today.

Dr. Manish Shah: So, just a little bit of background on the American Society of Hematology Annual Meeting. So, this is the 67th meeting. It'll be held in Orlando, December 6th through the 9th. It's the premier event in classical malignant hematology. ASH is the world's largest professional society concerned for blood disorders, both benign and malignant. It was founded actually in 1958. Initially, it was called The Blood Group. There was an informal meeting in Boston in 1957-- I looked this up for this podcast-- and then founded in 1958. It's grown to 17,000 members, it's really remarkable.

And these annual meetings, there's also ASCO, which is in June, are two of the premier meetings that allow for physicians to get together to exchange their research, exchange ideas, learn from each other and also connect with the partners in pharma. And these are the US-based meetings. There's also meetings in Europe and Asia. It's really quite a remarkable thing.

And this podcast is really focused on the top abstracts of ASH. And we'll start with Gail. Do you want to tell us about your top abstracts and what these mean to you?

Dr. Gail Roboz: I would be very happy to. The field of acute myeloid leukemia is absolutely exploding. So, AML is the most common acute leukemia among adults. It's still a rare disease, although you wouldn't know that from coming into my office or to our leukemia service. But this disease formerly occupied actually remarkably little space in the ASH Meeting, because for so many years there was so little going on. You talked about the start of ASH in the '50s. So, the '50s to late '60s was actually the development of a chemotherapy regimen for the treatment of acute myeloid leukemia, which is affectionately known as ‘7 and 3’, seven days of cytarabine, three days of anthracycline.

And at the time, again, from the '50s into the '60s, the development of this chemotherapeutic really changed AML from being absolutely uniformly deadly, to something where patients could go into remission. And there were even a few, albeit a small number, of cures. And the median age of AML is about 67 to 70 years old. So, older patients, although it hits a spectrum all the way from age zero to age a hundred plus. It is a dangerous disease. The bone marrow isn't taught in school as a vital organ, but it actually is a vital organ. You can't live without it. It produces white cells, red cells, and platelets. And when it gets taken over by acute leukemia, that is a life-threatening disease.

And the advent of 7 and 3 really changed things in that, at least for some younger patients, cure was possible, but for the majority of older patients, the chemotherapy was actually very difficult and debilitating. And not only that, it didn't work very well. So, there has been an arms race over all of these decades to try to improve 7 and 3. So if you can't beat 'em, join 'em, how do you make it better?

And more recently, there has been a challenge to the supremacy of 7 and 3 with the development of what we call non-intensive-- which is not really the right word-- but non-intensive hypomethylating agent-based treatment of AML, including a combination of either azacitidine or decitabine with a game-changing drug called venetoclax, which is an oral BCL-2 inhibitor.

Now, the plenary session at ASH-- so, AML made the plenary -- one of the plenary abstracts that is being presented is actually being called all kinds of fun names, like Survival of the Fittest, or Is 7 and 3 Finally Dead? And this is going to get a tremendous amount of attention, which is why I also selected it for discussion today, because this was a randomized trial, a phase II randomized trial, not phase III, which we are calling PARADIGM, which was checking to see whether this lower intensity regimen of azacitidine and venetoclax, which was developed primarily in older patients and in less physically fit patients who would be unable to take standard 7 and 3 chemotherapy.

How does aza-ven, which is what we colloquially call it, stand up to 7+3? The primary endpoint was met, and actually aza-ven looked a little better. The event-free survival, which was the primary endpoint, was met. There were higher rates of overall survival and remission. And this is a challenge to a 50-plus-year-old standard of care.

Now, the devil is, of course, in the details. We have not made a change in saying, "Don't worry about it. You don't need intensive therapy for AML." That's not what this trial says, but it looks like the ability to get patients into remission with a slightly gentler and safer induction regimen may actually result in increased rates of stem cell transplantation, including for patients all the way into their 60 and 70s. This remains to be seen. But it's a game-changer in that it looks like the number of patients who need intensive chemotherapy induction to get into remission is going to go down. And we have an alternative.

Dr. Manish Shah: So, that actually is incredible. I haven't treated leukemia for quite a while. And I remember 7+3. It sounds like people will be able to have this potentially new induction therapy with much less toxicity. Do you want to talk about the typical toxicity of aza-ven versus 7+3, just so our listeners can get the scope of the impact here?

Dr. Gail Roboz: The message of PARADIGM should not be, "Yay! AML is now an easy and safe disease to treat." That would actually be the wrong message. So, the problem with not having a working vital organ, and I keep repeating that because it's so helpful, I think, for patients and families and caregivers to understand what happens when your bone marrow doesn't work. Your bone marrow is basically infiltrated by these bad leukemic cells. You're not making white cells that are functional. You're subject to infections. You need transfusion support. The change of the chemotherapy regimen from a less easy to an easier regimen doesn't solve the problem of not having a working bone marrow.

However, what we call the extramedullary toxicity or the toxicities of the chemotherapy, everything from your hair falling out to nausea, to vomiting, to mucosal stress. Chemotherapy is like running a cheese grater on your intestinal tract. It opens you up for oral mouth sores, for diarrhea, for problems in the intestinal tract, all kinds of things that result typically in a three to four-week hospitalization for 7 and 3 that can often lead people to an intensive care unit. It's not easy. Azacitidine and venetoclax, also, you have risks to infection. You need transfusions. Again, the problem is that the bone marrow isn't working. But, the so-called extramedullary toxicities or these other side effects of very bad mucositis, damage to the GI tract, even rates of bad infections that lead you to the ICU are all better with the easier combination.

And then I can segue into my second abstract by bringing up a couple of points. I picked these so that they tell a story. There are many patients, for example, in the PARADIGM study who were excluded. And this is super important.

So, for example, the molecular targeted age of AML has really, really taken off. If you have something called a FLT3 mutation, which is in 25% of AML patients overall, you are standardly treated with 7 and 3, the "older chemotherapy" in combination with a FLT3 inhibitor. FLT3 patients were excluded from this study.

Similarly, patients with an NPM1 mutation, which is very common in AML patients and, in general, associated with a more favorable prognosis, these patients also were excluded from the PARADIGM study. And there is another abstract among my top three, which is looking specifically at a very, very cool and exploding area in AML of patients with molecularly defined diseases like NPM1 and FLT3, that we now have molecular monitoring techniques that can go down to one in a million – or even beyond -- cells to see which ones of those patients are completely cleared by existing therapies and, importantly, in the abstract that I mentioned for discussion, might be able to take some of those patients who are getting novel molecularly targeted agents that are not included in the PARADIGM study comparing standard therapies. Can you take novel molecularly targeted therapies, put people into what we call MRD negative or molecularly super deep remission and, even for some of those patients, possibly avoid stem cell transplantation?

So, the horizon in AML is looking brighter. We have better therapies that are more targeted that do allow some patients to avoid the toxicities of chemotherapy. But especially for the ones who might be curable with standard chemotherapy backbones, we are nervous about moving them into something which is less proven, which is a combination of lower intensity therapy and potentially novel agents.

So, it’s all about what’s your cure rate projected to be with a standard chemotherapy regimen. Can we safely move away from standard chemotherapy—which is something that Rick is going to talk about too, because across the hematologic malignancies we are trying very hard to dump standard chemotherapy in favor of better tolerated targeted agents.

So, in AML, who can we avoid 7 and 3 on? And I can say we avoid it on a lot of patients at Weill Cornell. And can you actually build on the azacitidine and venetoclax backbone with novel agents to make that backbone even better?

That is the segue to my final abstract, which is actually something that I am going to have the pleasure of presenting. We were the top accruer on this trial of a novel agent called ziftomenib, which is a menin inhibitor, in combination with azacitidine and venetoclax. So, what this is doing is taking a targeted molecule, which is active against KMT2A and NPM1. NPM1 commonly represented in AML; KMT2A, more rare but very deadly. And the question is, can we take a better tolerated backbone regimen and add on novel agents, whether they are FLT3 agents or anti-NPM1 menin inhibitors like ziftomenib, and take the patients in a safer way to molecularly deeper remissions? That is really the holy grail across the hematologic malignancies. And finally, AML is joining the party.

Dr. Manish Shah: That is really incredible. And I think you touched on a very important theme, which sounds like it's definitely true in AML. It's also true in solid tumors, is that when you are able to identify a target, we've seen in multiple studies that the earlier you hit the target, the better. And there is a potential to deescalate from cytotoxic chemotherapy, which is kind of a blunt instrument, to try to target the specific mutation that's causing the malignancy. I think that's really truly fantastic. And congratulations on your abstract. And these are fantastic abstracts in AML and really advancing the field.

Let's move on to the CLL and lymphoma space. Rick, what were the abstracts that you thought were going to be really important to highlight?

Dr. Richard Furman: Thank you, Manish. I want to really focus on two abstracts in CLL, and then four abstracts in diffuse large B-cell lymphoma that involved bispecifics. Very similar to what Gail just discussed with AML, in the hematologic malignancy space, and in particular with CLL, it's really past tense that we've moved beyond chemotherapy. And a paradigm change for us happened probably about 10 years ago when we really first saw the novel agents proven to be more effective and better tolerated than chemotherapy and actually move higher on the NCCN guidelines compared to all chemoimmunotherapy, such that no one with CLL should be getting chemotherapy in 2025/2026. The big question that we're now contended with is with a lot of fine tuning of our novel agent use.

So, our primary regimens are going to be BTK inhibitor directed therapies, which are often given as a continuous therapy versus a venetoclax plus obinutuzumab, which is a fixed duration therapy that's usually given for one to two years, and then sort of allows the patient to relapse with the idea that then you can actually use the treatment again or switch to an alternate therapy. Both of these are extremely efficacious and well tolerated, but whether or not doing a continuous BTK inhibitor therapy versus doing an intermittent BCL-2 inhibitor with venetoclax plus obinutuzumab, which is an anti-CD20 monoclonal antibody, really is a big question that a lot of us need to answer.

The offer to patients is often based upon what the physician thinks is the better therapy for the patient, but a lot of the time the decision is made based on patient preference for oral versus IV therapies, for remaining on a continuous therapy, or whether or not they just want to be done with therapy and get on with their lives. But we really don't have any comparative data until this time, and that I think is what's so important.

So, the plenary abstract that's being presented in CLL involves ibrutinib as a 420 milligram dose continuously until disease progression or unacceptable toxicity, versus venetoclax plus obinutuzumab, which is six months of combination oral venetoclax plus obinutuzumab intravenously, followed by six months of venetoclax as a single agent, versus venetoclax plus ibrutinib where patients are actually getting a three-month lead in of ibrutinib by itself, followed by 12 months of a combination venetoclax plus ibrutinib.

And in comparing these three, what the study did, and this was conducted by the German CLL Study Group, where they looked at 909 patients all randomized to each of the three different arms, really showed non-inferiority between the three different treatment regimens with progression-free survivals all of about approximately 80% with interestingly no difference in overall survival, but a little bit of a numerical advantage for ibrutinib and venetoclax-ibrutinib compared to venetoclax plus obinutuzumab. It's important to remember that there is no statistical difference between any of these treatment arms, and the take-home message from this trial is that these are all treatment regimens that are, at the currently available data, considered to be equally efficacious.

My perspective on this abstract is that the data will evolve, and we'll start seeing significant differences much further in the future. And fortunately with CLL, we are talking about considerations of impact on quality of life and length of life, five, ten years in the future after patients initiate therapy, which is a huge difference from where we were previously.

Dr. Manish Shah: So, the upshot of this abstract is that it sounds like the fixed duration targeted therapy might be non-inferior to continuous infusion, but you think that we need more time to follow these patients because the real devil is going to be five and ten years later. Is that right?

Dr. Richard Furman: Absolutely. And I think one of the big questions is going to be whether or not the anti-CD20 in the form of obinutuzumab actually really has a deleterious impact long-term on our patient's immune systems and whether or not this does set them up for infections further down the road, but also the fact that the fixed duration regimens do have this process of having patients get treated, their disease brought under control, and then allows the disease to relapse under the current paradigm of treatment for CLL. And I worry that, during the period of relapse, you do get clonal evolution. And while I believe 80% of CLL patients have clonally stable CLL and won't evolve, 20% really do have the potential to evolve. And evolution does include not just developing resistance mutations to the BTK inhibitors and venetoclax, but also the development of a Richter transformation, which still remains a highly lethal complication of CLL that we see in 10% of patients.

So from my perspective, the most important piece of information is going to be whether or not patients relapsing are being set up to subsequent failure. And that's something we're not going to see until patients get their second or third treatment, which will hopefully be far down the road.

Dr. Manish Shah: So, we have to follow these patients for longer.

Dr. Richard Furman: So, the second abstract though sort of addresses what we do in these patients when they do relapse, and what we do with the actual resistance. So, there's a group of agents called degraders, which take advantage of the ubiquitin-proteasome system and can actually target almost any protein for degradation within the cell. And one of the major reasons for resistance developing in CLL patients treated with BTK inhibitors is the development of a cysteine 481 serine mutation in the BTK gene that leads to an ability for the BTK inhibitors to bind to the BTK enzyme and therefore block the active pocket.

So, taking advantage of the proteasome system, we have a group of drugs called degraders that will target the enzymes to the proteasome through a totally different amino acid residue in the amino acid, and lead to the complete destruction of the protein. We currently have two in clinical development. One is the Nurix compounds, of which there are two, and the other one is BGB-16673. All three of these are extremely well-tolerated and really have demonstrated incredible specificity with regard to targeting the BTK enzyme, and that removes the first level of toxicity that we see with CLL patients. Because by not having these off-target effects, we totally avoid so many of the adverse events.

But what we're now looking at is actually the long-term response and in the populations that these responses actually occur in. So, looking at patients who have progressed on or relapsed after a BTK inhibitor and seeing how well these BTK inhibitors do, really gives us an idea about whether or not the BTK enzyme itself plays a role just as an enzyme conducting or adding phosphates to various other proteins, or whether or not it has a role as a structural protein and its degradation actually has a therapeutic benefit beyond just inhibiting it.

And where this really becomes so interesting is the group of patients who have what's called a PLC gamma 2 mutation and develop resistance to our BTK inhibitors. There's a bypass pathway now open that allows the cell to continue to have B-cell receptor signaling even in the absence of BTK enzymatic activity.

Looking at the data from this abstract overall, this was technically a phase I study that looked at 50, 100, 200, 350, and 500 milligrams of BGB-16673. And it was incredibly well tolerated with the adverse events really being exactly what you would expect. And the most expected and likely treatment-related adverse event was bruising, and this is because of the targeting of BTK and TEC in platelets with the BTK inhibition and platelets being on target and the TEC kinase inhibition of platelets being off target. But BTK and TEC have incredible amounts of homology that makes it almost impossible to target one without the other. So, incredibly well tolerated and demonstrated excellent activity in this patient population that really had shown resistance already to BTK inhibitors with overall response rates of 87%. And in the population overall and at what's become the phase II recommended dose of 200 milligrams, the overall response rate's 94%.

And interestingly, the phase II dose was chosen using the Optimus program, which is designed to choose the optimal dose, not the MTD or the maximum tolerated dose. So while I've had patients on 500 milligrams of BGB-16673, and they've tolerated it well and had no toxicities, we really found no additional benefits to going above 200 milligrams. So we've now started to molecularly select our doses, which I think is also an interesting step forward.

So here, I think the upside of this abstract, these are extremely well-tolerated agents, extremely effective. And then, the data's early, the 12-month progression-free survival was 80% in these patients that were heavily, heavily treated with many other agents. But it importantly shows that destroying BTK has an advantage over just inhibiting it, really suggesting that BTK plays a structural role. And this really opens up a great deal of other options for patients who do develop resistance to BTK inhibitors.

Dr. Manish Shah: Do you think that this could replace BTK inhibitors, because of the advantage that you mentioned of actually destroying the protein, the enzyme?

Dr. Richard Furman: I do think that the BTK inhibitors will be replaced by the BTK degraders, primarily because of the better tolerability profile and the improved safety profile. So with the current BTK inhibitors, besides seeing the bruising that is seen in all of them, ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib, we do see a lot of toxicities that are certainly much more serious.

So with ibrutinib, we see a lot of arrhythmias. We also see hypertension, myalgias, nail and hair changes. With acalabrutinib, we see headaches. With zanubrutinib, we also see hypertension that we saw with ibrutinib. And with pirtobrutinib, we ostensibly see an increased risk of bleeding. So with the degraders, all of a sudden all those adverse events fall by the wayside. So, we're hopeful that this will eventually become the upfront therapy just because of the tolerability profile and its already proven efficacy profile.

Dr. Manish Shah: Wow, that's really quite hopeful. I think that leads us to the other abstract in this space, the phase III FLAIR study, which is another BTK target, right?

Dr. Richard Furman: So, the FLAIR study is very analogous to what we saw with the CLL17 study. And in the FLAIR study, we were looking at fludarabine-based chemotherapy in the form of FCR versus ibrutinib as a single agent versus ibrutinib plus rituximab. And the FLAIR study is helpful in the sense that it adds to the idea about continuous versus intermittent therapy, like the CLL17 study. But the FLAIR study at this point in time has about 10 years of follow up. So, it gives us much longer follow up than the other studies.

The big issue with FLAIR is that it really was designed to compare chemoimmunotherapy to the novel agents. And so, that's sort of a question that's already been answered. Where I think the FLAIR trial's really going to teach us a lot in the future is related to the actual rate of clearance of the CLL. We don't know if when you treat someone with a BTK inhibitor or a BTK inhibitor plus an anti-CD20, whether or not you have a linear clearance of the CLL or whether or not there might be a plateau at the end.

And in our own data that will be shown at ASH, we have actually suggested that there's actually a plateau that occurs, and that the clearance of the CLL is not linear. And the FLAIR study was based on the idea that there is a linear clearance of the CLL and that you should be able to predict when a patient becomes cured of their CLL, not just having undetectable MRD.

And the idea was to double the time a patient was on treatment to get to undetectable disease, which is a level of CLL that's below one in 10,000 using flow cytometry. Doubling that time will get them down to a level that is estimated to be below 10 to the minus eight which is what is estimated to be tantamount to a cure. The problem is that the initial assumption of the linear clearance is probably not correct. And I think that's sort of the data that we now have, but seeing the results long term from the FLAIR trial will be very interesting.

Dr. Manish Shah: Both you and Gail talked about how we're really changing the paradigm. Over 20 years ago where we didn't talk about cure for these cancers. And now, we're beginning to. It's really, really remarkable.

Dr. Richard Furman: The approach is certainly that the patients need to just die with their disease, not from their disease. And so, the goal is not even cure. The goal is, of course, not bothering the patient at this point in time, and that's sort of a nice change in our motivation for selecting our therapies.

I wanted to talk about bispecifics and aggressive lymphomas, because the bispecifics really afford an opportunity to treat patients who are elderly and having comorbidities with what might be effectively curative therapy that doesn't involve adriamycin, which is the current mainstay of aggressive lymphoma therapy.

The big issue, of course, is going to be cytopenias and the risk of infection and death, but there's still a lot of issues with cardiotoxicity, mucositis, hair loss, and other factors that really have a huge impact on the patient's potential to survive therapy and also benefit from the therapy. So, a lot of physicians do shy away from using curative therapy in our elderly patients. Using these bispecifics and still being able to induce long-term remissions in the elderly infirm patients may actually provide a great strategy for our younger patients once we actually have longer term data.

So, the three abstracts I wanted to talk about looked at polatuzumab as an anti-CD79b drug conjugate in combination with rituximab as an anti-CD20 with glofitamab, which is an anti-CD3/CD20 bispecific in patients who had treatment naïve DLBCL that was ineligible for CHOP therapy due to comorbidities.

And importantly, we do see some adverse events with these bispecifics in the forms of a cytokine release syndrome and an immune cell effector-mediated neurotoxic syndrome. But with these agents, the adverse events for the CRS was 31% and for ICANS was only 4%. And importantly, these were almost all grade 1. So, it really shows that these drugs can be delivered safely and tolerably to patients who have immune systems that are still preserved.

These therapies were previously tested in patients who were all heavily pretreated, when the immune system, by its nature of being destroyed by so much prior chemotherapy, certainly may have been less likely to cause these immune-mediated reactions. So, we clearly know that we can now do it. And importantly, the overall response rate was above 90% in these patients with complete metabolic responses by Lugano criteria of 58%. And so, it really does show that this is highly effective therapy and therapy that may long-term lead to a great change in how we're treating these patients. The current progression-free survival at 15 months is 85%. But of course, we need much more follow-up to further look at these.

Two other bispecifics, epcoritamab and mosunetuzumab, were also looked at in elderly patients. And the data's very similar for these with regard to the tolerability and efficacy. There are some interesting subtleties that I think we need to work out between mosunetuzumab and epcoritamab. But it really does suggest that there's a non-chemotherapy approach to these patients who have aggressive lymphoma and can't tolerate chemotherapy. And one day, maybe even for those who could tolerate chemotherapy, to just be able to avoid the chemotherapy altogether.

The last I wanted to comment on was just a rapid dose escalation abstract that really is, I think, important because with these aggressive lymphomas, a lot of patients have trouble waiting for achieving the full dose during the dose escalation, which is designed to minimize these cytokine release syndromes and ICAN reactions. And looking in 30 patients who received glofitamab and  epcoritamab, doing rapid dose escalations that had reached a target dose for  glofitamab in 14 days versus 21 days, and for epcoritamab of six days versus 22 days, they showed only a slight increase in the rate of CRS and ICAN reactions, and almost all of them were just grade 1. So, it really suggests that we do have options for treating with a rapid escalation in a patient who needs to get very immediate control of their disease, that it's possible to do safely with these bispecific antibodies.

Dr. Manish Shah: I'm in awe with the advances in both leukemia and lymphoma. And it sounds like it's going to be a tremendous meeting. Gail, I'll come back to you. Any final thoughts as we end this podcast?

Dr. Gail Roboz: Well, I have to say that, I think, all of this incredible positivity should translate actually into a lot of excitement for patients to come in to participate even more in clinical trials. So on the one hand, we are very, very happy that a lot of these regimens are going to have patients be able to be treated closer to home potentially, and with wider access to reasonable drug therapy that doesn't necessarily require an academic center. But at the same time, everybody should try to be on a clinical trial because we are at such incredible moments across the hematologic malignancies. And the direct benefits and the rapid accrual to these clinical trials of novel agents is helping so many people. What I'm hoping is that it's going to actually encourage even more trial participation.

Dr. Manish Shah: Well, that's wonderful. Rick, final thoughts from you?

Dr. Richard Furman: It's great to be in a position where we're no longer having to work on increasing our efficacy of our treatment regimens, but we're now working on the tolerability. And it really is sort of nice to be able to take this step further where not only can we offer our patients cure or normal life expectancy, but we're now trying to fine tune it to the point where we can really do it with preservation of excellent quality of life.

Dr. Gail Roboz: A hundred percent, Rick. I just want to make sure that the audience doesn't conflate CLL and AML at all. You guys are in a much, much better position than we are in terms of offering so much more opportunity for very long-term survival. We want that too in AML. We want more cures and more discussions of 10 and 20 years. So, come on in for the trials.

Dr. Manish Shah: It's just been an honor to share this podcast with both of you with the advances that we've had in malignant hematology. For me, the themes are focused on the smarter we are with regard to targeting specific mutations in the diseases we treat, the better patients will fare. And that can lead to better survival and reduced toxicity.

And then, we're in an era where we're doing incredible things in medicinal chemistry to modify antibodies to make them bispecific or to make them as an antibody drug conjugate. And that evolution in drug development, I think, is truly a game-changer.

So with this, we'll close. I thank Dr. Gail Roboz, the Head of our Leukemia Program here at Cornell, and Dr. Rick Furman, the Head of our CLL Program. You can download, subscribe, rate, and review CancerCast on Apple Podcast, Spotify, YouTube, or online at weillcornell.org. We also encourage you to write to us at cancercast@med.cornell.edu with questions, comments, and topics you'd like to hear us cover in the future.

That's it for CancerCast, conversations about new developments in medicine, cancer care, and research. I'm your host, Dr. Manish Shah. Thank you for listening.

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