Healthcare Unfiltered
Healthcare Unfiltered is an honest, raw, timely podcast tackling any and all topics in healthcare that affect stakeholders. Dr. Chadi Nabhan uses his dynamic conversational skills to challenge his guests to address controversial and important topics. He also brings on world renowned experts to discuss clinical advances in medicine.
Healthcare Unfiltered
Episode 289 - Treating Leukemias: Past and Present With Hagop Kantarjian
Use Left/Right to seek, Home/End to jump to start or end. Hold shift to jump forward or backward.
In this special episode, Chadi sits down with one of the most influential figures in modern leukemia research and care: Hagop M. Kantarjian, MD, Professor and Samsung Distinguished Leukemia Chair in Cancer Medicine at The University of Texas MD Anderson Cancer Center. Dr. Kantarjian reflects on four decades of progress in leukemia treatment, discussing how the field has evolved from an era of limited therapeutic options to one transformed by groundbreaking scientific advances, while offering his perspective on risk stratification across favorable, less favorable, and high-risk leukemias.
The conversation spans chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML), including the promise of triplet and quadruplet regimens and the urgent need for better therapies in secondary leukemias. Combining historical perspective, clinical insight, and a vision for the future, this episode is a rare opportunity to hear from a physician-scientist whose work has helped shape the modern treatment landscape for patients with leukemia worldwide.
Check out Chadi’s website for all Healthcare Unfiltered episodes and other content. https://www.chadinabhan.com/
Watch all Healthcare Unfiltered episodes on YouTube. https://www.youtube.com/channel/UCjiJPTpIJdIiukcq0UaMFsA
It's Healthcare Unfiltered, and it's your host, Shadi Nabhan. Thank you for tuning in to this episode of Healthcare Unfiltered, folks. Thank you for supporting this podcast going on close to seven years now. Healthcare Unfiltered every Tuesday, week in and week out. I appreciate your support. As you know, we cover everything from clinical advances to healthcare policy, book authors, a lot of things in healthcare that we have covered over the years. And last year we've launched Healthcare Unfiltered Express. Healthcare Unfiltered Express focuses specifically on advances in clinical oncology, new papers, new findings. It's shorter format, about 10 to 15 minutes, that allows you to really get in touch with a lot of things that are happening right away. So check out both Healthcare Unfiltered and Healthcare Unfiltered Express. You can subscribe to both shows. They are available on all platforms from Amazon to Apple to Spotify, YouTube, and you can follow me on Twitter at ChaddyNabhan. And check out my Facebook page, my YouTube page, and my website, chattinabhan.com. Today's podcast is very special because I really host a legend, Dr. Hagob Kintargian. There's probably no one that is watching this show or listening to this show that does not know who Dr. Hagob Kintargian is. Arguably one of the most influential figures in oncology and hematology, and has really transformed how we treat malignant hematological disorders, specifically leukemias. Hagob has been the chair of the Department of Leukemia at MD Anderson Cancer Center, has held many leadership positions, and has won numerous awards. I really will not have time to list all of the awards that he won at ASCO and other societies. But needless to say, the first time I met Dr. Kantargian was in 2002, and I was preparing for the hematology oncology board, the George Washington board. And I recall listening to a lecture that he gave. I believe the lecture he gave was on AML, or uh it could have been CML. I don't really remember exactly. But it was so clear, was so obvious, was so easy to follow, so easy to understand. And I was always dreaming, I'm thinking, like, I wish I can one day give a lecture similar to the way Dr. Hagob Kantarjan delivers his lectures. And uh fast forward, I have been uh fortunate to learn a lot from Dr. Kantarjan, as so many of people who are listening here and who have really followed his work, as well as learn from him how we treat leukemia. Um, so I've asked Dr. Kantarjan to come on the show to really simplify how we approach leukemias, actually, which is not easy because we have so many types of leukemias, but interestingly, he suggested to me that he can actually cover that in less than 45 minutes. And he's gonna look at this from the risk stratification perspective into favorable, less favorable, and not favorable leukemias. And he's gonna lump all of these together under the leukemic disorders category. I am going to have Dr. Kantarjan in the future to come uh on the show and talk about his career path and about leadership, mentorship. There's so much to learn from this legend in hematology, Dr. Hagob Kantarjan. I think we are so fortunate and so grateful to have someone like Dr. Kantarjan, who has really dedicated his life to helping patients treat with leukemia and to mentoring many people who are interested in uh hematological malignancies. I don't think uh I I've given enough, I've given Dr. Kantarjan justice in terms of introducing him, but I am certain and confident that everybody who is watching this show or listening to this show know exactly who I am talking about. Without further ado, the myth and the legend, Dr. Hagob Kantarjan on Healthcare Unfiltered. Well, folks, uh it's really a very um important day for me because not only that this is the first time Dr. Hagob Kantarjan comes on my show, Healthcare Unfiltered, but um everybody knows who Dr. Cantarjan is, and I have been a big fan for 25 years. He has mentored a lot of us uh who are interested in malignant hematology. So, Hagob, it's uh truly an honor to have you on my humble show.
SPEAKER_00Likewise, Dr. Naban.
SPEAKER_01Uh when you tell me Dr. Nabhan, that's very interesting. But um, before we get started, Hagob, uh um a bit about you in terms of what got you, take us through memory lane for 30 years. What got you into leukemia, into malignant hematology?
SPEAKER_00So, as you may know, I was uh trained at the American University of Beirut in Lebanon, and this is where people absorb knowledge and then they apply it. I came for an elective uh fellowship at MD Anderson in 1978. And this is where I discovered that perhaps 90% of the knowledge in cancer will be obsolete 10 years later. And MD Anderson allowed individuals in training to expand with their vision and to take chances. Uh uh, you do high-risk uh but also high-benefit uh approaches to therapy. And many of those fail, but ultimately some of them will become the new standards of care. And having an approach of innovation uh allows a faster pace of cancer research. Uh at MD Anderson I met Dr. Emil J. Freyrak, uh Dr. McCready Keating, and many of the giants in leukemia research, and I decided to come back and stay at MD Anderson. So that's what I did. In 81, I came and trained as a fellow at MD Anderson, and then I stayed on faculty from 1983 till the present time.
SPEAKER_01You're a lifer, you're a lifer at MD Anderson. And um it's amazing to see what has happened uh in the treatment of leukemia. And that's really the subject of today's podcast. We wanted to talk about the evolution of leukemia treatment and leukemia research, how things were 40 years ago, 1981, when you first started, and now we are 2026. So let's just start by how when you first started, how how were things? How was your thinking process? How was research at the time, and then how did things evolve?
SPEAKER_00Right. So, just as um as a background, when we think of leukemias, we divide them in our mind into the acute and chronic leukemia, and that's based on the course of the diseases if untreated. So acute leukemias, patients lived two years untreated, uh, two two patients lived about one to two months if untreated. The chronic leukemias, they lived about uh a couple of years, and then we divide them by the cell of origin, so in simple ways, myeloid versus lymphoid. So you have four main kinds of leukemia: acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, and chronic lymphocytic leukemia, and then you have subsets like APL and core binding factor, acute myeloid leukemia as part of AML, and hairy cell leukemia, which is a cousin of chronic lymphocytic leukemia. But I I like to divide them based on how the research has advanced from 1981 till now. So if you think about them, in 1981, most of the leukemias were in what is called unfavorable category, meaning their five-year survival was less than 30%. There was one intermediate leukemia, acute promyelostic leukemia, and that's because uh ensacyclines were discovered in the 70s. So with anthracyclines, acute bromyostic leukemia had a five-year survival of about 40%. And then there were no favorable leukemias. There were no leukemias where you could say that the five or 10-year survival is uh above uh 70%. So when I started in 1981, the two acute leukemias, AML and ALL, were curable at a rate of 20% with intensive chemotherapy. Uh, these are the adult ALL. In the chronic leukemia, both CML and CLL were incurable, and the five-year survival was about also um 10 to 20 percent. You fast forward to today, most of the leukemias have shifted to the favorable category, meaning we expect their survival to be over 70% or 80% at five to ten years. Then we have an intermediate group of leukemia where also there are substantial subsets. And now we uh have seen that among the unfavorable leukemia, there's only two simple categories: the older patients with AML and patients with maybe TP53 and MECO. So, if you like, I could take you through the progress in each of these entities and uh going from the most favorable to the least favorable, but also to show that there's no one path for curing cancer. A lot of it is trial and error, and also much of it is deciphering the pasophysiology of particular leukemias and then developing drugs that target those pasophysiologists.
SPEAKER_01I would love to do that. Um, and before we do it, Hagob, uh, I was gonna what was the rate limited? What was the catalyst event that you think led to this acceleration in um in change? Is it uh the uh you know genomic sequencing? I mean, what what was it you think?
SPEAKER_00I think deciphering the pathophysiology, we started actually around uh the mid-80s when people started talking about cancer genes or oncogenes, starting with the MEC and with the other oncogenes. And then in the 2000s, uh, with actually deciphering the whole um uh human genome and then looking at cancer genomes and finding abnormalities. So, to give you a few examples, um, when in acute myelid leukemia, when they developed the first leukemia genome, they identified maybe two or three abnormalities. It was IDH1, uh, TP53 was well known, and maybe there was a third mutation. Now we know that there's a whole spectrum of uh more than 100 mutations, and many of those mutations are targetable. And this is what led, for example, to develop FLIP-3 inhibitors, IDH inhibitors, menine inhibitors, the development of venetoclax as a BCL2 inhibitor. So all these were derived by understanding the pathophysiologic mechanisms of particular leukemias, uh, either through their metabolic functioning or through particular mutations.
SPEAKER_01Amazing. Okay, let's uh let's pick uh your leukemia of choice and just go through uh how this transformed from unfavorable to a favorable, maybe.
unknownRight.
SPEAKER_00So, what I'm gonna do for simplicity is start with the best leukemias, the most favorable today, and I'm gonna outline seven of them with different uh modalities that led to their high potential cure. Then I'll go to the intermediate leukemias and then we'll leave the unfavorable till the last. So when you think of the favorable leukemias, these are leukemias where the five to ten year survival is over 80%. The simplest example is hairy cell leukemia, and the discovery was empirical because gladribine was developed for the treatment of T cell malignancies. But then there was one patient on the phase one study with hairy cell leukemia who received the treatment and went home to die because of lack of response, and that patient came back six months later in complete remission. So one empirical recovery in the clinic led to the potential cure of hairy cell leukemia. Uh, so now uh the way we treat hairy cell leukemia is for with five days of cladribine, then we use the CD20 antibody retoxima, we give it weekly four or eight times, and the 10-year progression-free survival is 90 to 95 percent. So this is a leukemia that is easier to treat than even a pneumonia, because pneumonias you need a longer course of antibiotic, more toxicity, and a higher mortality. So that's one example of a simple kind of leukemia that has a high cure rate and where we cannot do better than this. And the interesting point is the pathophysiology was discovered after uh those findings. So now we know that they are related to the BRF mutation, and people are developing BRF inhibitors, but uh the uh train has left the state the station. There's nothing better than cladarbine and retoximab as frontline curative syrup. The second leukemia, which is highly curable, is actually a subset of acute myeloid leukemia, acute promyelotic leukemia. So in 1981, a third of the patients died during the induction from DIC, and the cure rate with chemotherapy was 40%. The Chinese in the late 1980s started reporting on two drugs which were not chemotherapy. One was ATRA, which is a vitamin A analog, and the other one was arsenic trioxide, which is a poison. And when those studies came out of China, we decided at MD Anderson in 2000 to combine these agents as a non-chemotherapy regimen for leukemia. And people thought we're crazy because when we presented the data at the beginning, the uh the APL officionados thought that uh using a regimen without Iderubicin and ATRA was criminal. Yeah, yeah. As the data evolved, then the same APL experts took the MD Henderson regimen, atra arsenic trip side, compared it in a randomized trial 12 years later to Atra-Idarubicin, and they found that the non-chemotherapy regimen developed at MD Henderson was better, highly curative, with a 10-year survival of 90%. And this is now called the Lococo regimen after the person who did the randomized trial. Now, the third kind of highly curable leukemia is core binding factor acute myeloid leukemia. So these are patients with translocation A21 or inversion 16. And here the uh curative approach was in two steps. The first step was the discovery of high-dose RRC as opposed to standard RRC, that increased the cure rate from 30 to 50 percent, and then the discovery and the implementation of Gem2zumar, the CD133 antibody, which increased the cure rate from 50 to 80 percent. So, in core binding factor leukemia, we did not make major targeted discoveries, we just collected two kinds of therapies in a synergistic fashion that led to the cure rate of 80 percent in these patients.
SPEAKER_01Amazing stories, by the way, the cladribine story with that one patient, the APL one, and this one as well. Just the stories behind the science, amazing.
SPEAKER_00Now, the next two leukemias are very interesting because these two leukemias were driven by deciphering the pathophysiology of these leukemias. And these include CML and CLN. So, in chronic myeloid leukemia, before 2000, we treated the patients with allogenic transplant or with interferon, and the average survival was about five years. In 2000, Dr. Brian Drucker, collaborating with Novartis, developed the first BCR able tyrosine kinase inhibitors, ematin. And following that, because we saw that patients were developing resistance to EMATNIB with mutations in the able kinasal domain, we developed the more potent second generation TKIs, so desatineb, bosutineb, nilotinib, and then we developed the third generation TKIs, which were even more potent and could also uh suppress the T3015 I clones. So now you have all these TKIs which were implementing in the front line, and now patients with chronic myeloid leukemia are expected to have a normal lifespan. So the 10-year survival increased from 10% to 90%, and uh we are working on strategies to uh be able to stop the therapy in most of the patients, what we call treatment fear emission or a molecular cure. So today, in 100% patients with CMN, we expect probably 90 to 95 of them to live their normal life, and we expect about 30 to 40 percent to be able to stop therapy after five years of complete molecular cure. Now, how and and they don't have to be treated for years, they have to be treated for about five to seven years, not for a lifetime. Now, what where are we going to make progress in CML? Personally, I think that if we develop instead of BCR inhibit BCR-able inhibitors, if we develop BCR-able degraders and combine them with the BCR-able inhibitors, then potentially we could develop a combined regimen that's given for a year in the form of pills that would cure most of the patients with CML.
SPEAKER_01What would be the difference? Like in degrading degraders, they just basically get rid of the domain completely?
SPEAKER_00No. So the inhibitors suppress the signal, but the cells that have the signal can remain dormant in a small proportion, and when you stop the TKI, it comes back. The degraders get into the BCR able and destroy it. So they can destroy dormant cells which are resistant to BCR able inhibitors, and this is not science fiction. So to get you back to uh the evolution of cancer research, at the beginning we had the first uh option, which was surgery, then came radiation therapy, then came chemotherapy, then came the targeted therapies in the form of antibodies or the first BCR able kinase inhibitor, and then we had the checkpoint inhibitors, a form of immunotherapy, and then the CART cells. And now I think the sixth arm of cancer therapy are going to be degraders, tumor target degraders. So the example is in chronic lymphocytic leukemia, for example, where we know that the BCR uh that the bruton tyrosine kinase degraders may be more potent than the BTK inhibitors, and they could replace them and be more effective. So that's the story in CML that I would like to see with the development of BCR-able degraders that we could add to BCR-able inhibitors and perhaps cure chronic myeloid leukemia at a high percentage. The other chronic leukemia is, of course, chronic lymphocytic leukemia. And today, when you read the textbooks, people say that chronic lymphocytic leukemia is still incurable. I personally think CLL is curable if you consider cure, meaning that the patient gets a treatment, the disease disappears, and it never comes back in the rest of the lifetime of the patient. So, where did the breakthrough come from? It came in 2014, after we understood the role of the BTK and the BCL2 in prolonging the survival of the CLL cells. So BTK inhibitors were developed, the netoclex was developed. At MD Anderson, we combined both. Of them for two years of therapy, and the first study was with um uh a brutin and venetoclax given for two years, and we have treated over 200 patients, and with uh all the patients being off therapy for a minimum of five years, we have only 20 patients who have relapsed with a five-year survival of 97 percent. So, again, CLL is the sixth form of favorable leukemias where the five to ten year survival is over 70 percent.
SPEAKER_01The only thing though, Hagob is we usually we classify CL as lymphoma. You gotta be careful here.
SPEAKER_00It used to be classified as lymphoma until Michael Keating discovered the activity of fluerabine. So we stole them from the lymphoma people and we developed FC and FCR, and now the BTK inhibitors. So we think of CLL as a leukemia rather than a lymphoma at MD Anders.
SPEAKER_01Yeah, uh yeah, I know that. That's I had to say it though.
SPEAKER_00So then there are two additional leukemias but that became very favorable as of I would say 2010-2017. And these are the two subsets of ALL, adult ALL. So, as you know, in childhood ALL, you give three years of intensive chemotherapy and you cure about 80% of the children, but that's really not manageable in poorer countries and in the community setting. In adult ALL, using the same three years of intensive chemotherapy, we were able to have a five-year survival of about 50 percent. In 2000, we started in Philadelphia positive ALL to add the BCR-able kinase inhibitors to chemotherapy. So that was the first inflection point. In 2017, we found that blinatumal was better than chemotherapy, and we had by then developed ponatineib, which is a very potent BCR-able kinase inhibitor. So in 2017 at MD Anderson, we combined ponatinib with blinatumumal in a simultaneous schedule, and now we're reporting a five-year survival of 90% without intensive chemotherapy and with less than 5% of the patients requiring an allogenic transplant. So that was how long is this regimen?
SPEAKER_01Two years?
SPEAKER_00So the regimen is given for five courses of blinatumad. And unfortunately, today we have to give five years of ponatinem because we want both the PCR and the NGSMRD to be negative. And we're starting to do like CML. After five years of a complete molecular response, we're starting to stop therapy. And in about 17 patients where we did this, zero of the 17 have relapsed. So the treatment is going to be about five years. Now we can improve on this because so far we have not used the CART cells instead of allogenic transplant. So it is possible that in the future we'll do the uh ponatineib or a better BCR-able kinase inhibitor. We'll do the five uh courses of Blinna, and then we will do a consolidation with CART cell, which may allow us to discontinue the uh ponetinib sooner rather than after five years. So that's the plan for chronic my uh for uh Philadelphia positive acute lymphocyth leukemia. But if you think about it, before 2000, uh uh Philadelphia positive ALL was a fatal disorder. It was a death sentence. Today it's the easiest of one of the easier leukemia to treat. Now, another subset is B cell ALL, where we developed both uh blinatumumab and inotuzumab. We added them to the chemotherapy, and now we have five-year survivals, which are very close to the five-year survival in childhood ALL, so 85 uh percent. And this is with about half of the chemotherapy, but with the addition of those two antibodies. Uh, personally, I think five years from now we may treat ALL like lymphomas with six courses of chemotherapy with blinatumumumab inotumumab, followed by the CART cells, and then stop the treatment. So rather than three years of intensive chemotherapy, about six to seven months of milder chemotherapy with the targeted therapies with a potentially very high Q rate.
SPEAKER_01Amazing. So these are the seven, right? We did the we did the three APL, hairy cell, core binding factor, we did CML, CLL, and then we did the uh the last uh so these are the seven favorable leukemias.
SPEAKER_00These are the seven favorable. The intermediate have two categories. The older patients with ALL where using mini CVD, Ponatineblina, we have now a five-year survival of 50%. And then the younger patients with AML, where instead of three plus seven, we're using a more intensive therapy, the FLAG IDA venetoclax or the CLIA venetoclax, and we are having five-year survival rates of 70%. But these patients still require allogenic transplant and remission, and we're starting to add the targeted therapies. So the FLIT-3 inhibitors, the um uh IDH inhibitors, the menin inhibitors, of course, on top of the venetoclax, uh, in addition to the chemotherapy. So these are the two intermediate leukemias, older ALL and younger AML, where actually the five-year survival has exceeded 40%. And in the younger AML, it's about 70% in our hands.
SPEAKER_01Now the last quick question the men inhibitors are um are being incorporated into frontline as part of trials, or are they right now ready for prime time in frontline?
SPEAKER_00Uh no, so today they are part of trials uh because we have not incorporated them yet into the community to be added to the chemotherapy. And the question is: do you add them to 3 plus 7? Do you add them to CLIA venetoclax, or do you add them to the lower intensity regimens that we use in older AML, like Ladribine, Lodos RSC venetoclax, or isacytidine venetoclax? So this is where there's a bit of a struggle in terms of implementing safe regimens in uh acute myeloid leukemia, where you pile up more targeted therapies onto the intensive chemotherapy venetoclax. So now there's a group of leukemia doctors who are saying, why do we need the intensive chemotherapy at all? Can we use lower intensity therapy as we do in older AML with hypomethylating agent and the venetoclax to which we add the targeted therapies? I prefer cladribine lodos RS venetoclax because it's better than azocitidine venetoclax. It is a low intensity regimen, and we can add those targeted therapies to that. So you're going to see a broad range of research in AML where different investigators do different things, either adopting intensive chemotherapy with targeted therapy, or using azocitine venetoclax in triplet or quadruplate regimens, or at MD Anderson pushing for the cladribine lodos RSC venetoclax, to which we add a regimen in a quadruplate fashion, such as cladribine lodos RSE venetoclax with a FLIT3 inhibitor, with an IDH inhibitor, with a menine inhibitor, either simultaneously or in a sequential fashion.
SPEAKER_01So now this takes us to the poor ones.
SPEAKER_00So let's talk about the poor ones. So the poor ones are patients over the age of 60 with acute myelid leukemia. No, so we excluded APL, we excluded core binding factor, acute myelid leukemia. So these are the older patients with acute myelid leukemia. And um you see the leukemia experts twisting themselves around trying to find which patients would be unfit for intensive chemotherapy to give them HMA venetoclass. But if you look at the SEER data, it's very simple. The mortality with any form of chemotherapy, if you're under 60, is about 10% during the induction. If you are 60 to 75, it goes to 30 percent. And if you are over 75, it goes to 50 percent. This is the four-week mortality in community practice by this year data. Now, of course, in cancer centers, the mortalities are less, but this they still range between say 10 or 15 percent during the induction. So um what we need to do is come up with regimens where the mortality is very low and where you can add things to increase the Q rate. So people started with the hypomethylating agent. We had them since 2006, minimal benefit. In 2017, the HMA venetoclux regimen was developed and became a new standard of care. But when we look at the long-term follow-up with isacytidine venetoclux, in all the unfit patients, the three-year survival is only 25%. So then we are working on two strategies. The first one are triplet regimens uh with an HMA, and I prefer all are decitabine because then you can have a total oral therapy with dicitabine, venetoclax, and the third targeted therapy, or you can do cladribine lodos RSC venetoclax.
SPEAKER_01What's uh what's an attractive third target, in your opinion, in this situation?
SPEAKER_00So the third target when you do, say, azacytobene, decytabine, venetoclax will be a flit 3 inhibitor if the patient is flithery mutated, an IDH inhibitor if they are IDH1 or 2 mutated, and a menin inhibitor if they have uh um uh if they have uh a translocation 11 Q23 uh abnormality, but also there are other uh rearrangements that uh can benefit from the menine inhibitors or possibly the possibility of what we call a menine signature, meaning uh an overexpression of particular cytokines that could respond to menine inhibitors. Now we also found that menine inhibitors synergize with FLIT3 inhibitors and they synergize with venetoclax. So now instead of using triplet therapy, we're trying to advocate for safe quadruplet therapy where we use the FLIT 3 inhibitors even in FLIT-3 wild type, if they have a FLIT-3-like signature, and we add the venetoclax and possibly the menon inhibitor as indicated by the signature. So there's a signature called MIS-1 signature that uh indicates that MIS-1 overexpression could be sensitive to menon inhibitors. So these are the triplet regimens or quadruplate regimens that we're testing in older AML, and these may find a foothold in the younger patients in the future, as was shown by Dr. Amir Fatih when he combined when he compared isocitidine venetoclux to 3 plus 7 and showed the very exciting data at the Ash meeting.
SPEAKER_01You know, I uh I actually love the fact that you looked at the leukemias this way. I honestly haven't thought of it this way because you cannot combine the ALL, AML, CML, CL, all of them together in under one big umbrella, and we're defining them based on the risk category. It's almost like a different way of looking at leukemic disorders, myeloid disorders, if you will.
SPEAKER_00Correct. And and actually, this way of a classification may be uh more pertinent because then you start thinking of subsets of leukemia rather than the umbrella of acute versus chronic and myeloid versus lymphoid. So you talk about leukemia, what is the pathophysiology, and what can we add to the treatment that will increase the potential curate?
SPEAKER_01There's one leukemia you didn't address a little bit. Maybe we can spend a minute or two on it, which is secondary leukemia or treatment-related leukemia. I presume obviously this fits in the high risk unless things have changed.
SPEAKER_00No, actually, the three leukemias where we need something urgently are TP53, acute myeloid leukemia. Nothing has worked, and that's about 10 to 15 percent of AML. MECOM rearranged leukemias. So these are patients with translocation 3 to Q26 with a rearrangement. These are not common, that's these are about 1 to 2 percent, but they have a horrible outcome. And then what you mentioned, the treated secondary AML. So patients with either MDS or myeloproliferative neoplasms who are treated and progress to AML. These three categories of acute myelukemia, we have nothing in our armamentarium that works so far. So what we need to do is develop either targeting strategies or strategies which are agnostic to the pathophysiology. So, for example, if you develop uh N-K cellular therapy for minimal residual disease or possibly uh some form of immune therapy that eradicates residual disease. But we do not have yet good clues as to how to treat those three terrible leukemias that nothing has worked on so far.
SPEAKER_01Well, no retirement, I guess, until you figure this out. Uh so um my question to you is uh if we're having this conversation maybe a couple of years from now, are you what's your futuristic look on leukemia? Are you optimistic? Do you sometimes look, I mean, I'm pragmatic and I'm realistic. There are times where you think, you know, we've done all we can. I'm not really sure we're gonna be able to find something for TP53 unless you literally have a target against the TP53, which we tried. I think I remember there's several molecules that were hypothesized to target the TP53, but they really never seen it. Yeah. Um, I mean, what's your futuristic look? How are we heading in the next couple of years?
SPEAKER_00So I think in the more favorable leukemias, we are going to be able to do much better. I think CML, if we discover a BCR-able degrader that's effective and safe, we will cure CML maybe with one year of combined therapy and the CLL. We have better uh BTK inhibitors, we have the BTK degraders, we have better BCL2 inhibitors coming along. So I think CLL will be potentially highly, highly curable with maybe one and a half to two years of dose combinations. In ALL, both Philadelphia positive and the B cell ALL, I think by adding additional antibodies like CD20 by specific T cell engagers or safer uh TKIs uh than ponatinate, for example, or verambatinin, we're going to be able to increase the chance of a cure in both B cell ALL and uh pre-BALL. And don't forget, we're starting to use the CAR T cells as a consolidation rather than uh rather than allogenic transplant. In acute myeldochemia, we need to discover more targets and better targeted therapies. So, for example, if we discover one good pan RAS inhibitor, this will be a major breakthrough because a lot of the patients with AML who relapse, relapse with a RAS-based wave mutation. And now we know that there's a very effective KRAS inhibitor in pancreatic cancer. So if we have a good pan RAS inhibitor that we can export to acute myelogleukemia, it will elevate the potential cure rate across all AMS. I do not know what will work in TP53, but there is already one molecule, an antibody, that targets the uh TP53 with the mutation at 220, and it's working very well. But there are more, uh about 90 mutations along the TP53 molecule. So I don't know that we can develop one inhibitor for each of those mutations. We have to have a better approach to TP53. With the MECOM, we're working on the pathophysiology, and we think we have something that might work. And with the treated secondary AML, that's also a big problem uh that we need to tackle.
SPEAKER_01Yeah, but the advances are historic. I mean, and this is not an easy thing to do. I mean, I I re you know, when I was a fellow, um I could not treat ALL. I tried, it was impossible. And and I was at a university setting, and it was my biggest nightmare when I had to take care of an ALL patient. Not because things were not working, it was because you still had to do so much treatment and very intensive therapy, and it and the outcome was so dismal. Uh, and it's just amazing to see this. Um, I go any other questions I should have asked you pertaining to the treatments of leukemias. You you did promise you're gonna come back where we're gonna talk about mentorship, leadership, and other aspects are not science, because a lot of people could learn from you and your your journey. But anything about leukemias that we should have talked about that I forgot asking you about?
SPEAKER_00No, I think uh we pretty covered it much. Uh actually, I have an Asco Post uh editorial uh that I co-wrote with Dr. Freirach, the late Dr. Freyrak. It came out this month, so people who are interested can look at it and it's essentially goes in a summary form through what we talked about.
SPEAKER_01Yeah, if you send me a link, I will uh put it in the notes because this will uh we're we're taping this just for listeners and viewers. This is being taped before ASCO, but it's not is not going to come, it's gonna come out probably early July. So uh we'll be close enough to Soho. Uh so this will be we'll strategically put it before Soho. And how many years now you've been doing Soho, Hagob?
SPEAKER_00So Soho started under a different name. It was started by Michael Keating, he called it leukemia, the next question. Uh, and this was like uh maybe 20 years ago, and then we made it hematologic malignancies the next questions, and then we changed it to the Society of Hematologic Oncology, which started in 2012, I think. So we're gonna be our 13th or 14th year now.
SPEAKER_01Congratulations. I uh I I I will try to visit with you guys in Houston. It just happens around Labor Day, and it had like you you need to uh you need to make the meeting around my schedule.
SPEAKER_00I insist that you come to Soho because you'll you'll be able to interview so many people.
SPEAKER_01Yes, I'm gonna be we have to we have to form a collaboration between Soho and Healthcare Unfiltered. God willing. Dr. Hagop Kantarjan, the myth, the legend, the master of leukemia in his in the flesh here on Healthcare Unfiltered. Thank you so much for coming on.
SPEAKER_00Very kind of you to invite me. Thank you.
SPEAKER_01It means a lot to me that you gave Healthcare Unfiltered this exclusive. Uh, folks, you can follow me on Instagram, Shadi underscore healthcare unfiltered, on YouTube, on X, or formerly known as Twitter, and let me know what you think. You can also suggest ideas, topics, and absolutely be engaged and uh follow all of the progress on Healthcare Unfiltered. And don't forget to check out also Healthcare Unfiltered Express and let your friends, colleagues know about both shows. Drop a brief review. This allows a lot of people to discover this podcast and always let me know how I'm doing. Before I let you go, I'm gonna leave you with a saying by Lebanese poet Khalil Jibran. Out of suffering have emerged the strongest souls, the most massive characters are seared with scars. Until next time.