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In this episode, we delve into the key clinically relevant abstracts in leukemia and myeloid neoplasms with Dr. Jayastu Senapati from the MD Anderson Cancer Center. Here are the links to the abstracts we discussed: Older AML: Ven+HMA vs 7+3Abstract 450: https://ash.confex.com/ash/2024/webprogram/Paper210320.htmlAbstract 971: https://ash.confex.com/ash/2024/webprogram/Paper202801.htmlAbstract 969: https://ash.confex.com/ash/2024/webprogram/Paper199267.htmlVenetoclax resistance mechanismshttps://pubmed.ncbi.nlm.nih.gov/39478230/FLAG-GO vs FLAG-IDA https://ashpublications.org/blood/article/144/Supplement%201/1513/532742/Gemtuzumab-Ozogamicin-Added-to-Fludarabine CPX-351: Abstract 55: https://ash.confex.com/ash/2024/webprogram/Paper207094.htmlAbstract 60: https://ash.confex.com/ash/2024/webprogram/Paper200413.htmlMenin Inhibitors Abstract 211 https://ash.confex.com/ash/2024/webprogram/Paper194384.htmlAbstract 212 https://ash.confex.com/ash/2024/webprogram/Paper207106.htmlAbstract 213 https://ash.confex.com/ash/2024/webprogram/Paper194827.htmlAbstracts 214 https://ash.confex.com/ash/2024/webprogram/Paper198218.htmlAbstract 215 https://ash.confex.com/ash/2024/webprogram/Paper198218.htmlAbstract 216 https://ash.confex.com/ash/2024/webprogram/Paper204375.html FLT3 inhibitors Abstract 221: https://ash.confex.com/ash/2024/webprogram/Paper201595.html MDS Abstract 349: https://ash.confex.com/ash/2024/webprogram/Paper194510.html ATRA in MDS: https://ash.confex.com/ash/2024/webprogram/Paper200433.html
Dr. John Sweetenham and Dr. James Foran discuss the evolving treatment landscape in acute myeloid leukemia, including new targeted therapies, advances in immunotherapy, and the current role for allogeneic transplantation. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast. There has been steady progress in the therapies for acute myeloid leukemia (AML) in recent years, largely based on an increasing understanding of the molecular mechanisms which underlie the disease. On today's episode, we'll be discussing the evolving treatment landscape in AML. We'll explore risk group stratification, new targeted therapies, advances in immunotherapy for AML, and also a little about the current role for allogenic transplantation in this disease. I'm delighted to welcome Dr. James Foran to this discussion. Dr. Foran is a professor of medicine and chair of the Myeloid Malignancies and Blood and Marrow Transplant Disease Group at the Mayo Clinic Comprehensive Cancer Center. He's based in Jacksonville, Florida. Our full disclosures are available in the transcript of this episode. James, it's great to have you join us on the podcast today, and thanks so much for being here. Dr. James Foran: I'm delighted and thank you for the invitation. Thank you very much. Dr. John Sweetenham: Sure, James, let's get right into it. So, our understanding of the molecular mechanisms underlying AML has resulted not only in new methods for risk stratification in this disease, which have added refinement to cytogenetics, but also has resulted in the development of many new targeted agents. Understanding that this is a complex area of investigation, and our time is somewhat limited, can you give us a high-level update on the current state of the art in terms of how risk factors are being used for treatment selection now? Dr. James Foran: Absolutely. I think in the past, you know, we had things broken down pretty simply into make a diagnosis based on morphology, do cytogenetics, break patients into the groups of those who were more likely to benefit from therapy – so-called favorable risk – those where the intensive therapies were less likely to work – so-called poor adverse risk, and then this large intermediate group that really had variable outcomes, some better, some worse. And for a long time, the progress was in just identifying new subtle cytogenetic risk groups. And then, late 1990s, we began to understand that FLT3 mutations or NRAS mutations may be more adverse than others that came along. In the first part of this millennium, in the, you know, 2000-2010 range, a lot of work was being done to understand better or worse risk factors with single genes. The ability to do multiplex PCR, and then more recently NGS platforms, have allowed us to really look at many genes and identify many mutations in patients. At the beginning that was used just to sort of refine – who did a little better, who did a little worse with intensive therapy – helped us decide who may benefit more from an allogeneic transplanter for whom that would not be necessary. But the good news is that really, we're now starting to target those mutations. One of the first molecularly targeted treatments in leukemia was FLT3 mutations, where we knew they were adverse. Then along came targeted treatments. I was involved in some of those early studies looking at sunitinib, sorafenib, more recently midostaurin, now quizartinib, FDA approved, and gilteritinib in the relapse refractory setting. So we're moving into a state where we're not just refining prognosis, we're identifying targets. You know, it's been slow progress, but definite incremental progress in terms of outcomes by looking for FLT3 mutations, then looking for IDH mutations, and more recently, mutations involving NPM1 or rearrangement of what we used to call the MLL gene, now the lysine methyltransferase 2A or KMT2A rearrangement, where we now have targets. And it's not just for refinement of prognosis, but now we're identifying therapeutic targets for patients and ways to even look for measurable residual disease which is impacting our care. Dr. John Sweetenham: That's great, James. And I'm going to expand on that theme just a little bit and perhaps ask you to elaborate a little bit more on how the introduction of these new therapies have specifically impacted frontline therapy. And a couple of ancillary questions maybe to go along with that: First of all, is ‘7+3' a standard therapy for anybody in 2025? And maybe secondly, you know, could you comment also maybe briefly on older patients with AML and how you think maybe the treatment landscape is changing for them compared with, say, 5 or 10 years ago? Dr. James Foran: I'll start with the therapy and then work my way back. So we've had ‘7+3' cytarabine daunorubicin or cytarabine anthracycline since 1976, and we're still using it as the backbone of our intensive therapy. There is still an important role for it, particularly in younger or fitter patients, and particularly for those with intermediate or favorable risk genetic groups or cytogenetic risk groups just because we achieve high rates of remission. Our 30-day induction mortality rates are lower now than they were 10 and 20 years ago. Our supportive care is better. And we still have a busy inpatient hospital service here at Mayo Florida and my colleagues in Rochester and Arizona as well giving intensive therapy. So that remains the backbone of curative therapy for younger adults. We are trying to be a little more discriminating about who we administer that to. We are trying to add targeted agents. We know from, now, two different randomized trials that the addition of a FLT3 inhibitor, either midostaurin or more recently quizartinib, has a survival advantage in patients with a FLT3 mutation, or for quizartinib, a FLT3/ITD mutation. And so yes, ‘7+3' remains important. Off protocol for somebody who just comes in with acute leukemia in a 40-year-old or 30-year-old or even early 60s and fit, we would still be considering ‘7+3' therapy and then waiting for an expedited gene mutation panel and an expedited cytogenetics panel to come back to help us discriminate is that a patient for whom we should be giving a FLT3 inhibitor? I think there's a little more nuance about when we do a day 14 bone marrow, do they really matter as much anymore? I still do them. Some of my colleagues find them less important. But we're still giving intensive therapy. We're still giving high-dose ARA-C consolidation for younger patients who achieve complete remission. In older adults, it's a different story. You know, it was only in the early part of the 2000s – 2004, 2007 range – where we really got buy-in from randomized studies that low-dose therapy was better than no therapy. There was a lot of nihilism before then about therapy for older adults, especially over age 75. We know that low-dose ARA-C is better than nothing. It looked like azacitidine was better than ARA-C or at least equivalent or slightly better. But with the advent of venetoclax it was a game changer. I ran a national randomized study of intensive therapy in AML. It was the last national randomized study of intensive therapy in older patients right before venetoclax got approved. And we were very excited about our results, and we thought we had some really interesting clinical results. And suddenly that's a little bit obsolete in patients over 70 and particularly over age 75 because of the high remission rates with azacytidine venetoclax or hypomethylating agents, so-called HMAs and venetoclax and the survival advantage. Now, it's not a home run for everybody. We quote 60% to 70% remission rates, but it's a little different based on your cytogenetics and your mutation profile. You have to continue on therapy so it's continuous treatment. It's not with curative intent, although there are some people with long-term remission in it. And the median survival went from 10 months to 15 months. So home run? No, but definitely improved remissions, meaningful for patients off transfusions and better survival. So right now it's hard to find an older adult who you wouldn't give azacitidine and venetoclax or something similar, decitabine, for instance, and venetoclax, unless somebody really was moribund or had very poor performance status or some reason not to. And so ‘7+3' is still relevant in younger adults. We're trying to get better results with ‘7+3' by adding targeted agents and azacitine and venetoclax in older adults. I think the area of controversy, I guess there are two of them, is what to do in that overlap age between 60 and 75. Should people in that age still get intensive therapy, which we've used for years – the VIALE-A trial of aza-venetoclax was age 75 plus – or with cardiac comorbidities? And I think if you're 68 or 72, many of us are starting to bias towards aza-venetoclax as generally being better tolerated, generally being more outpatient, generally being slow and steady way to get a remission. And it doesn't stop you from going to transplant for somebody who might still be a candidate. The other area of controversy is somebody under 60 who has adverse cytogenetics where we don't do very well with ‘7+3,' we still give it and we might do just as well with decitabine venetoclax. A lot of us feel that there's equipoise in the 60 to 75 group where we really can ask a question of a randomized study. Retrospective studies might suggest that intensive therapy is a little better, but there are now a couple of randomized studies happening saying, “Can we replace ‘7+3' in that intermediate age with aza-venetoclax?” And for younger adults similarly, we're looking to see how we apply that technology. Those are the areas where we're really trying to investigate what's optimal for patients and that's going to require randomized trials. Dr. John Sweetenham: Oh, that's great, thank you. And I'll just extend that question a little bit more, particularly with respect to the new targeted therapies. How much are they impacting the treatment of these patients in the relapse and refractory setting now? Dr. James Foran: Oh, they're definitely impacting it. When I trained and probably when you trained, AML was still a medical emergency. But that was the thing that you admitted to the hospital immediately, you started therapy immediately. The rule was always that's the one thing that brings the fellow and the consultant in at night to see that new patient on a Friday or Saturday. Now, we'll still admit a patient for monitoring, but we try not to start therapy for the first three or five or seven days if they're stable, until we get those genetics and those genomics back, because it helps us discriminate what therapy to pursue. And certainly, with FLT3 mutations, especially FLT3/ITD mutations, we're adding FLT3 inhibitors and we're seeing a survival advantage. Now, on the surface, that survival advantage is in the range of 7% or 10%. But if you then pursue an allogeneic transplant in first remission, you're taking disease where we used to see 30%, 40% long-term survival, maybe less, and you're pushing that to 60%, 70% in some studies. And so we're now taking a disease that– I don't want to get off topic and talk about Ph+ ALL. But that's a disease where we're actually a little excited. We have a target now, and it used to be something really adverse and now we can do a lot for it and a lot about it. The other mutations, it's a little more subtle. Now, who knew until 2010 that a mutation in a sugar metabolism gene, in isocitrate dehydrogenase, or IDH was going to be so important, or even that it existed. We know that IDH1 and IDH2 mutations are still a minority of AML, certainly less than 10% to 15%, maybe overall. But we're able to target those with specific IDH1 and IDH2 inhibitors. We get single-agent responses. There are now two approved IDH1 inhibitors on the market. We don't yet have the randomized data that adding those to intensive therapy is better, but we're getting a very strong hint that it might be better in older adults who have an IDH mutation, maybe adding those is helpful and maybe adding those to low-intensity therapy is helpful. Those studies are ongoing, and we're also trying with low-intensity treatments to add these agents and get higher remission rates, deeper remissions, longer remissions. I think a lot of work has to be done to delineate the safety of that and the long-term efficacy. But we're getting hints it's better, so I think it is impacting. The other area it's impacting is when you pick up adverse mutations and those have crept into our classification systems like an ASXL1 mutation or RUNX1 mutation for instance, or some of the secondary AML mutations like BCOR and others, where that's helping us discriminate intermediate-risk patients who we think aren't going to do as well and really helping us select a group who's more likely to get benefit from allogeneic transplant or for whom at least our cure rates without allo transplant are low. And so I think it's impacting a lot. Dr. John Sweetenham: Great. And I'm going to pick up now, if I may, on a couple of things that you've just mentioned and continue the theme of the relapsed and refractory setting. We've started to see some reports which have looked at the role of immune strategies for patients with AML, in particular CAR T or NK cells. Can you comment a little on this and let us know whether you think either these two strategies or other immune strategies are likely to have a significant role in AML in the future? Dr. James Foran: They are, but I think we're still a step behind finding the right target or the right way to do it. If you think of allogeneic transplantation as the definitive immune therapy, and we know for adverse AML we can improve survival rates and cure rates with an allotransplant, then we know inherently that immune therapy matters. And so how do we do what they've done in large cell lymphoma or in CD19 targeting for B cell malignancies? How do we bring that to acute myeloid leukemia? There have been a number of efforts. There have been at least 50 trials looking at different targets. CD33, CD123, CD7, others, CLL-1. So, there have been a number of different trials looking at how to bind a CAR T or a CAR T construct that can be active. And we have hints of efficacy. There was kind of a provocative paper in the New England Journal of Medicine a year ago in April of last year from a Chinese group that looked at a CD7-based CAR T and it was 10 patients, but they used CD7 positive acute leukemia, AML or ALL and had a CD7-targeted CAR T and they actually incorporated that with a haploidentical transplant and they had really high remission rates. People tolerated it quite well. It was provocative. It hasn't yet been reproduced on a larger scale, but the strong hints that the strategy is going to work. Now, CD33 is a little tricky to have a CAR T when CD33 is expressed on normal hematopoietic cells. CD123 likewise. That's been something where there's, I think, still promise, but we've struggled to find the trials that make that work. Right now, there's a lot of interest in leveraging NK cells and looking, for a couple of reasons, but NK cells are attractive and NK cell markers might be attractive targets. NK cells might have similar degrees of immune efficacy. It's speculative, but they are likely to have less cytokine release syndrome and less neurotoxicity than you see with CAR T. And so it's kind of attractive to leverage that. We have had some ongoing trials looking at it with bispecifics and there certainly are trials looking at it with CAR NK-based strategies. One of the antigens that people looked at is the NK group 2D. NK group 2D or NKG2D is overexpressed in AML and its ligands overexpressed. And so that's a particular potential target. So, John, it's happening and we're looking for the hints of efficacy that could then drive a pivotal trial to get something approved. One of the other areas is not restricting yourself just to a single antigen. For instance, there is a compound that's looking at a multi-tumor-associated antigen-specific T-cell therapy, looking at multiple antigens in AML that could be overexpressed. And there were some hints of activity and efficacy and actually a new trial looking at a so-called multi-tumor associated antigen-specific T cell therapy. So without getting into specific conflicts of interest or trials, I do think that's an exciting area and an evolving area, but still an investigational area. I'll stop there and say that we're excited about it. A lot of work's going there, but I'm not quite sure which direction the field's going to pivot to there. I think that's going to take us some time to sort out. Dr. John Sweetenham: Yeah, absolutely. But as you say, exciting area and I guess continue to watch this space for now. So you've mentioned allogeneic stem cell transplants two or three times during this discussion. Recognizing that we don't have an imatinib for AML, which has kind of pushed transplant a long way further back in the treatment algorithm, can you comment a little on, you know, whether you think the role of stem cell transplantation is changing in AML or whether it remains pretty much as it was maybe 10 years ago? Dr. James Foran: By the way, I love that you use imatinib as an introduction because that was 6 TKIs ago, and it tells you the evolution in CML and you know, now we're looking at myristoyl pocket as a target, and so on. That's a great way to sort of show you the evolution of the field. Allogeneic transplant, it remains a core treatment for AML, and I think we're getting much smarter and much better about learning how to use it. And I'm just going to introduce the topic of measurable residual disease to tell you about that. So I am a little bit of a believer. Part of my job is I support our allogeneic transplant program, although my focus is acute myeloid leukemia, and I've trained in transplant and done it for years and did a transplant fellowship and all that. I'm much more interested in finding people who don't need a transplant than people who do. So I'm sort of looking for where can we move away from it. But it still has a core role. I'll sidestep and tell you there was an MDS trial that looked at intermediate or high-risk MDS and the role of allogeneic transplant that shows that you about double your survival. It was a BMT CTN trial published several years ago that showed you about double your three-year survival if you can find a donor within three months and get to a transplant within six months. And so it just tells you the value of allotransplant and myeloid malignancy in general. In AML we continue to use it for adverse risk disease – TP53 is its own category, I can talk about that separately – but adverse risk AML otherwise, or for patients who don't achieve a really good remission. And I still teach our fellows that an allotransplant decreases your risk of relapse by about 50%. That's still true, but you have to have a group of patients who are at high enough risk of relapse to merit the non-relapse mortality and the chronic graft versus host disease that comes with it. Now, our outcomes with transplant are better because we're better at preventing graft versus host disease with the newer strategies such as post-transplant cyclophosphamide. There are now new FDA-approved drugs for acute and chronic graft versus host disease, ruxolitinib, belumosudil, axatilimab now. So we have better ways of treating it, but we still want to be discriminating about who should get it. And it's not just a single-minded one-size-fits-all. We learned from the MORPHO study that was published in the JCO last year that if you have FLIT3-positive AML, FLIT3/IDT-positive AML, where we would have said from retrospective studies that your post-transplant survival is 60% give or take, as opposed to 15% or 20% without it, that we can discriminate who should or shouldn't get a transplant. Now that trial was a little bit nuanced because it did not meet its primary endpoint, but it had an embedded randomization based upon MRD status and they used a very sensitive test of measurable residual disease. They used a commercial assay by Invivoscribe that could look at the presence of a FLT3/ITD in the level of 10 to the minus 5th or 10 to the minus 6th. And if you were MRD-negative and you went through a transplant, you didn't seem to get an advantage versus not. That was of maintenance with gilteritinib, I'll just sort of put that on there. But it's telling us more about who should get a transplant and who shouldn't and who should get maintenance after transplant and who shouldn't. A really compelling study a year ago from I don't know what to call the British group now, we used to call them the MRC and then the NCRI. I'm not quite sure what to call their studies at the moment. But Dr. Jad Othman did a retrospective study a year ago that looked at patients who had NPM1 mutation, the most common mutation AML, and looked to see if you were MRD positive or MRD negative, what the impact of a transplant was. And if you're MRD negative there was not an advantage of a transplant, whereas if you're MRD positive there was. And when they stratified that by having a FLT3 mutation that cracked. If you had a FLT3 mutation at diagnosis but your NPM1 was negative in remission, it was hard to show an advantage of a transplant. So I think we're getting much more discriminating about who should or should not get a transplant by MRD testing for NPM1 and that includes the patients who have a concomitant FLT3 mutation. And we're really trying to learn more and more. Do we really need to be doing transplants in those who are MRD-negative? If you have adverse risk genetics and you're MRD-negative, I'll really need good data to tell me not to do a transplant, but I suspect bit by bit, we'll get that data. And we're looking to see if that's really the case there, too. So measurable residual disease testing is helping us discriminate, but there is still a core role of allogeneic transplant. And to reassure you, compared to, I think your allotransplant days were some time ago if I'm right. Dr. John Sweetenham: Yes. Dr. James Foran: Yeah. Well, compared to when you were doing transplants, they're better now and better for patients now. And we get people through graft versus host disease better, and we prevent it better. Dr. John Sweetenham: That's a great answer, James. Thanks for that. It really does help to put it in context, and I think it also leads us on very nicely into what's going to be my final question for you today and perhaps the trickiest, in a way. I think that everything you've told us today really emphasizes the fact that the complexity of AML treatment has increased, primarily because of an improved understanding of the molecular landscape of the disease. And it's a complicated area now. So do you have any thoughts on what type of clinical environment patients with AML should be evaluated and treated in in 2025? Dr. James Foran: Yeah, I want to give you a kind of a cautious answer to that because, you know, I'm a leukemia doctor. I work at a leukemia center and it's what we focus on. And we really pride ourselves on our outcomes and our diagnostics and our clinical trials and so on. I am very aware that the very best oncologists in America work in private practice and work in community practice or in networks, not necessarily at an academic site. And I also know they have a much harder job than I have. They have to know lung cancer, which is molecularly as complicated now as leukemia, and they have to know about breast cancer and things that I don't even know how to spell anymore. So it's not a question of competence or knowledge. It's a question of infrastructure. I'll also put a little caveat saying that I have been taught by Rich Stone at Dana-Farber, where I did a fellowship a long time ago, and believe Rich is right, that I see different patients than the community oncologists see with AML, they're seeing different people. But with that caveat, I think the first thing is you really want to make sure you've got access to excellence, specialized hematopathology, that you can get expedited cytogenetics and NGS testing results back. There was a new drug, approved just a few months ago, actually, for relapsed AML with a KMT2A rearrangement, revumenib. We didn't talk about the menin inhibitors. I'll mention them in just a second. That's a huge area of expansion and growth for us. But they're not found on NGS platforms. And normal cytogenetics might miss a KMT2A-rearrangement. And we're actually going back to FISH panels, believe it or not, on AML, to try to identify who has a KMT2A-rearrangement. And so you really want to make sure you can access the diagnostic platforms for that. I think the National Referral Labs do an excellent job. Not always a really fast job, but an excellent job. At my institution, I get NGS results back within three days or four days. We just have an expedited platform. Not everybody has that. So that's the key, is you have to be able to make the diagnosis, trust the pathologist, get expedited results. And then it's the question of trying to access the targeted medications because a lot of them are not carried in hospital on formulary or take time to go through an insurance approval process. So that's its own little headache, getting venetoclax, getting gilteritinib, getting an IDH1 inhibitor in first line, if that's what you're going for. And so I think that requires some infrastructure. We have case managers and nurses who really expedite that and help us with it, but that's a lot of work. The other piece of the puzzle is that we're still with AML in the first month and maybe even the second month. We make everybody worse before we make them better. And you have to have really good blood bank support. I can give an outpatient platelet transfusion or red cell transfusion seven days a week. We're just built for that. That's harder to do if you're in a community hospital and you have to be collaborating with a local blood bank. And that's not always dead easy for somebody in practice. So with those caveats, I do find that my colleagues in community practice do a really good job making the diagnosis, starting people on therapy, asking for help. I think the real thing is to be able to have a regional leukemia center that you can collaborate with, connect with, text, call to make sure that you're finding the right patients who need the next level of diagnostics, clinical trial, transplant consults, to really get the best results. There was some data at ASH a couple of years ago that looked at – the American Society of Hematology and ASCOs had similar reports – that looked at how do we do in academic centers versus community practice for keeping people on therapy. And on average, people were more likely to get six cycles of therapy instead of three cycles of therapy with azacitidine venetoclax at an academic center. Now, maybe it's different patients and maybe they had different cytogenetics and so on, but I think you have to be patient, I think you have to collaborate. But you can treat those patients in the community as long as you've got the infrastructure in place. And we've learned with virtual medicine, with Zoom and other platforms that we can deliver virtual care more effectively with the pandemic and beyond. So I think we're trying to offer virtual consults or virtual support for patients so they can stay in their home, stay in their community, stay with their oncologists, but still get access to excellent diagnostics and supportive care and transplant consults, and so on. I hope that's a reasonable answer to that question. It's a bit of a nuanced answer, which is, I think there's an important role of a leukemia center, and I think there's a really fundamental role of keeping somebody in the community they live in, and how we collaborate is the key to that. And we've spent a lot of time and effort working with the oncologists in our community to try to accomplish that. John, I want to say two other things. I didn't mention in the molecular platforms that NPM1 mutations, we can now target those on clinical trials with menin inhibitors. We know that NPM1 signals through the Hoxa9/Meis1 pathway. We know that similar pathways are important in KMT2A rearrangements. We know that there are some other rare leukemias like those with NUP98 rearrangement. We can target those with menin inhibitors. The first menin inhibitor, revuminib, was approved by the FDA for KMT2A. We have others going to the FDA later this year for NPM1. There are now pivotal trials and advanced expanded phase 1/2 studies that are showing 30% response rates. And we're looking to see can we add those into the first-line therapy. So, we're finding more targets. I'll say one last thing about molecular medicine. I know I'm a little off topic here, but I always told patients that getting AML was kind of like being struck by lightning. It's not something you did. Now, obviously, there are risk factors for AML, smoking or obesity or certain farm environments, or radioactive exposures and so on. But bit by bit, we're starting to learn about who's predisposed to AML genetically. We've identified really just in the last five or eight years that DDX41 mutations can be germline half the time. And you always think germline mutations are going to cause AML in a younger patient, but the median age is 60 to 70 just like other AMLs. They actually might do pretty well once they get AML. We've reported that in several papers. And so we're trying to understand who that has a RUNX1 mutation needs germline testing, who with a DDX41 needs germline testing. And we're trying to actually come up with a cleaner pathway for germline testing in patients to really understand predisposition, to help with donor selection, to help with family counseling. So I think those are other areas where a leukemia center can contribute for somebody in who's community practice to understand genomic or genetic complexity in these patients. And we're starting to develop the databases that support that. Dr. John Sweetenham: Yeah, great. Thanks, James. I loved your answer about the clinical environment too. And I know from a patient-centric perspective that I know that patients would certainly appreciate the fact that we're in a situation now where the folks taking care of them will make every effort to keep them close to home if they possibly can. I want to thank you, James, for an incredible review of a very complex subject and I think you did a great job. I think we all will have learned a lot. And thanks again for being willing to share your insights with us today on the ASCO Daily News Podcast. Dr. James Foran: John, it's my pleasure. And as you know, I'll do anything for a latte, so no problem at all. Dr. John Sweetenham: Okay. I owe you one, so thank you for that. And thank you to our listeners for your time today. You'll find links to the studies we've discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers: Dr. John Sweetenham Dr. James Foran Follow ASCO on social media: @ASCO on Twitter ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. John Sweetenham: No relationships to disclose Dr. James Foran: Stock and Other Ownership Interests: Aurinia Pharmaceuticals Consulting or Advisory Role: Peerview, CTI BioPharma Corp, Remix Therapeutics, Cardinal Health, Medscape, Syndax, Autolus Therapeutics Research Funding (Inst.): Chordia Therapeutics, Abbvie, Actinium Pharmaceuticals, Kura Oncology, Sellas Life Sciences, Novartis, Roivant, Celgene/Bristol-Myers Squibb, Astellas Pharma, SERVIER Travel, Accommodations, Expenses: Peerview
Os opioides são analgésicos potentes, usados para tratar dores pontuais ou crônicas. A equipe do pesquisador francês Cyril Rivat, do Instituto de Neurociências, em Montpellier, no sul da França, busca entender por que moléculas como a morfina pioram a dor de certos pacientes ou não fazem efeito. Taíssa Stivanin, da RFI em ParisOs estudos do neurocientista francês são feitos em parceria com pesquisadores do Inserm (Instituto de Pesquisas Médicas da França), CNRS (Centro Nacional de Pesquisas Científicas) e a empresa Biodol Therapeutics. A startup, que tem um contrato de colaboração com a equipe francesa, visa criar um medicamento experimental contra esses efeitos adversos. Eles também estão presentes nas dores neuropáticas, que surgem após lesões nos nervos, medula ou cérebro. A expectativa é que o futuro remédio, ao bloquear um receptor cerebral chamado FLT3, possa controlar as reações indesejadas que decorrem do uso da morfina. Os testes clínicos da fase 1 com humanos devem começar em 2025 na França. "A Biodol Therapeutics obteve um financiamento em 2024 para lançar a primeira fase dos testes clínicos com humanos. A inclusão dos participantes começou em dezembro, com voluntários", explica o cientista francês.De acordo com o especialista, "o primeiro objetivo é avaliar os possíveis efeitos tóxicos de um composto químico que terá como alvo o receptor FLT3". A primeira fase, diz Cyril Rivat, deve terminar em 2025. "Se tudo correr bem, vamos organizar a fase 2, que deverá analisar os efeitos da substância na dor neuropática crônica." MecanismosA resistência aos efeitos da morfina está relacionada a vários mecanismos neurobiológicos complexos, que ainda estão sendo identificados pela Ciência e estão relacionados ao receptor cerebral onde age a morfina. “Estamos avançando, mas ainda há questões em aberto”, diz o cientista. Diversos estudos mostram que a estimulação frequente do receptor FLT3 acaba diminuindo o efeito da morfina, que fica restrita à parte interna da membrana cerebral. Esse mecanismo altera sua função analgésica, que é eliminar a dor.A morfina também pode, em alguns casos, provocar um aumento da sensação dolorosa, como demonstrou um estudo recente do pesquisador francês, publicado na revista Nature Communications. “Pode ser totalmente paradoxal, mas podemos explicar esse fenômeno do ponto de vista neurobiológico. Trata-se de um mecanismo de adaptação do organismo, que tenta se defender contra o uso dos opioides", detalha. O neurocientista francês lembra que nem todas as pessoas estão propensas a essas reações adversas."A morfina continua sendo uma das melhores moléculas que existem no tratamento contra a dor. Há usuários que se tornam dependentes químicos, como revela a crise dos opioides nos Estados Unidos, mas a molécula continua sendo uma referência e demonstra uma grande eficácia”. Dores neuropáticasEm suas pesquisas sobre o tema, que tiveram início em 2018, o cientista francês descobriu, em testes celulares no laboratório e com animais, que esses dois efeitos após o uso da morfina – aumento da dor e resistência ao efeito analgésico - também eram observados nos pacientes com dores neuropáticas. O cientista também constatou que, ao bloquear o receptor FLT3, a morfina voltava a fazer efeito. Nos animais, o resultado foi ainda mais impressionante. “Conseguíamos bloquear a resistência, o aumento da dor e melhorávamos os efeitos analgésicos da morfina.” Os mecanismos do receptor FLT3 nas dores neuropáticas também são alvo de uma colaboração entre o pesquisador francês e o cientista brasileiro Thiago Cunha, da Faculdade de Medicina de Ribeirão Preto. "O professor Thiago Cunha também é um especialista das dores neuropáticas, mas estuda as interações que chamamos de neuro-imunes, entre o sistema nervoso e o sistema imunológico", explica. "O receptor FLT3 é ativado por um neuromediador produzido pelas células imunitárias. Estamos tentando entender melhor essa interação existente entre esse neuromediador e o receptor FLT3".
Harry Paul Erba, MD, PhD - New Tools, New Considerations: Optimizing Our Approaches to Managing Newly Diagnosed FLT3-Mutant AML
Harry Paul Erba, MD, PhD - New Tools, New Considerations: Optimizing Our Approaches to Managing Newly Diagnosed FLT3-Mutant AML
Harry Paul Erba, MD, PhD - New Tools, New Considerations: Optimizing Our Approaches to Managing Newly Diagnosed FLT3-Mutant AML
Harry Paul Erba, MD, PhD - New Tools, New Considerations: Optimizing Our Approaches to Managing Newly Diagnosed FLT3-Mutant AML
Harry Paul Erba, MD, PhD - New Tools, New Considerations: Optimizing Our Approaches to Managing Newly Diagnosed FLT3-Mutant AML
Harry Paul Erba, MD, PhD - New Tools, New Considerations: Optimizing Our Approaches to Managing Newly Diagnosed FLT3-Mutant AML
BUFFALO, NY- October 23, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on October 11, 2024, entitled, “Gene regulatory network and signalling pathway rewiring: How blood cancer cells shift their shapes to evade drug treatment.” As highlighted in the paper, Acute Myeloid Leukemia (AML) is a complex and diverse disease caused by multiple mutations in genes that regulate transcription and growth. These mutations lead to extensive rewiring of the gene regulatory network (GRN), which alters the identity of hematopoietic stem and progenitor cells, ultimately blocking normal myeloid differentiation. A key feature of AML is the presence of mutations in growth factor receptor and signaling genes, such as FLT3, KIT, and RAS. Notably, FLT3 is one of the most commonly mutated genes in AML, with around 25% of cases showing an internal tandem duplication (ITD) that causes the receptor to remain constantly active. In their paper, researchers Constanze Bonifer and Peter N. Cockerill from the Institute of Cancer and Genomic Sciences at the University of Birmingham, UK, and the Murdoch Children's Research Institute, Royal Children's Hospital in Melbourne, Australia, discuss recent publications from their group addressing this issue through a multi-omics study. The authors investigated how gene regulatory networks (GRNs) in FLT3-ITD patients were rewired compared to normal cells and in response to FLT3 inhibitor treatment. Several key findings stood out, including: 1) Mapping of open chromatin regions revealed that patients initially responsive to FLT3 inhibition showed significant rewiring of their GRNs, forming new connections between transcription factors (TFs) and target genes, while non-responsive patients did not; 2) Chromatin immunoprecipitation (ChIP) experiments showed that drug treatment led to the loss of binding of RUNX1, the master regulator of hematopoiesis, and the MAP-Kinase (MAPK)-inducible TF AP-1; 3) Disruption of AP-1 binding via a dominant-negative version of the TF (dnFOS) also abolished RUNX1 binding at hundreds of sites, indicating that RUNX1 binding is AP-1 dependent; and 4) Inhibition of both AP-1 and RUNX1 led to a pronounced cell cycle block. “In summary, drugs that target individual signalling pathways in AML often fail to stop proliferation malignant growth, due to the wide variety, redundancy and cross talk between multiple pathways regulating and differentiation.” DOI - https://doi.org/10.18632/oncotarget.28662 Correspondence to - Constanze Bonifer - constanze.bonifer@mcri.edu.au Video short - https://www.youtube.com/watch?v=5c_uT6aE36A Sign up for free Altmetric alerts about this article: https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28662 Subscribe for free publication alerts from Oncotarget: https://www.oncotarget.com/subscribe/ Keywords - cancer, acute myeloid leukemia, gene regulatory networks, aberrant growth factor signaling, transcription, RUNX1/AP-1 axis About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh
In this episode of the Oncology Brothers podcast, hosts Drs. Rahul and Rohit Gosain are joined by Dr. Mikkael Sekeres, Professor of Medicine and Chief of the Division of Hematology at the University of Miami. Together, they explore the complex landscape of acute myeloid leukemia (AML), discussing the latest advancements in diagnosis, treatment options, and risk stratification. Key topics included: • The importance of molecular testing in AML diagnosis and treatment planning • The role of intensive induction chemotherapy and the classic 7+3 regimen • New oral therapies, including FLT3 inhibitors and hypomethylating agents combined with venetoclax • Strategies for managing elderly or frail patients who are ineligible for intensive chemotherapy • The significance of measurable residual disease (MRD) in treatment decisions and transplant eligibility • Insights into managing side effects and complications associated with AML treatments Join us for an informative discussion that sheds light on the evolving treatment landscape of AML and the importance of personalized care in oncology. Don't forget to check out our other episodes on hematological malignancies, and we look forward to seeing you at ASH 2024! Subscribe to our channel for more insights and updates in the world of oncology! Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com
In this episode, listen to Professor Eunice S. Wang, MD, share her clinical insights and takeaways on new data for acute myeloid leukemia (AML) presented at the 2024 ASCO annual meeting and the EHA 2024 Congress including:Data from the prospective, single-center phase Ib/II study of FLAG-IDA plus venetoclax in newly diagnosed or relapsed/refractory AML Phase I/II study of oral decitabine/cedazuridine with venetoclax and gilteritinib in patients with newly diagnosed and relapsed/refractory FLT3-mutant AMLA retrospective comparison of abbreviated course 7+7 vs standard HMA plus venetoclax doublet in older/unfit patients with newly diagnosed AML Multisite randomized trial of a collaborative palliative and oncology care model for patients with AML and myelodysplastic syndromes (MDS) receiving nonintensive therapyFinal 5-year results from the phase II pivotal cohort of olutasidenib for IDH1-mutated AML Post hoc analyses of outcomes in patients with AML and MDS-related changes who received oral azacitidine maintenance therapy in the phase III QUAZAR AML-001 studyFirst-in-human phase I/II of the menin-MLL inhibitor DSP-5336 in patients with R/R acute leukemia: updated results from the dose escalation phase A phase Ib study of the menin-KMT2A inhibitor bleximenib in combination with venetoclax and azacitidine in R/R AML with alterations in KMT2A or NPM1 Program faculty:Eunice S. Wang, MDChief, Leukemia and Benign Hematology ServiceProfessor of OncologyRoswell Park Comprehensive Cancer CenterBuffalo, New YorkCourtney DiNardo, MD, MSCEProfessor of MedicineDepartment of LeukemiaMD Anderson Cancer CenterHouston, TexasResources:To download the slides associated with this podcast discussion, please visit the program page:https://bit.ly/4bvJGij
If you've studied the hematopoietic system malignancies—all the leukemias, lymphomas, and plasma cell disorders—you probably feel like you've been hit with the good old medical school fire hose. Now's a good time to take a step back from all the details, make sure that you remember the underlying framework, and pull together some information that connects several different diseases. In this brick, we'll revisit some of the hematopoietic diseases that we often talk about in pairs: acute vs chronic leukemias, benign lymph node diseases vs lymphoma, and low-grade vs high-grade lymphomas. Also, in case you haven't already done this on your own, we'll pull together all the important translocations, their respective diseases, and the reasons why we should remember them. After listening to this AudioBrick, you should be able to: Compare and contrast acute and chronic leukemias. Compare and contrast the morphologic features of benign follicular hyperplasia and follicular lymphoma. Compare and contrast the morphologic and clinical features of low-grade and high-grade lymphomas and give examples of each. Know the following translocations and name the disease (and prognostic significance, if any) associated with each: t(8;21), t(15;17), inv(16), 11q23, FLT3 mutation, t(9;22), t(11;14), t(14;18), and t(8;14). You can also check out the original brick on Hematopoietic Malignancies: Putting It All Together from our Hematology collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks. After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology. *** If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts. It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn how you can access over 150 of our bricks for FREE: https://usmlerx.wpengine.com/free-bricks/
Christian Récher, MD, PhD - Practical Considerations for FLT3 Inhibitors in Acute Myeloid Leukaemia: Optimising Our First-Line Approaches With Current and Novel Therapeutics
Christian Récher, MD, PhD - Practical Considerations for FLT3 Inhibitors in Acute Myeloid Leukaemia: Optimising Our First-Line Approaches With Current and Novel Therapeutics
Christian Récher, MD, PhD - Practical Considerations for FLT3 Inhibitors in Acute Myeloid Leukaemia: Optimising Our First-Line Approaches With Current and Novel Therapeutics
Christian Récher, MD, PhD - Practical Considerations for FLT3 Inhibitors in Acute Myeloid Leukaemia: Optimising Our First-Line Approaches With Current and Novel Therapeutics
An early study of patients (Phase I/II) with acute myeloid leukemia found that a new three-drug combination therapy greatly improved outcomes—both in patients with relapsed or refractory disease and as initial therapy. The new research involved adding quizartinib that targets fms-related tyrosine kinase 3 (FLT3) oncogene. Mutations of FLT3 are present in nearly a third of all AML tumors. The internal tandem duplication mutation of FLT3, in particular, is associated with poor prognosis in AML. So, it was hypothesized that targeting FLT3 could help in treating FLT3-mutated AML. First author Musa Yilmaz MD, Associate Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, has been talking with OncTimesTalk correspondent Peter Goodwin.
The process of identifying which patients with acute myeloid leukemia (AML) can benefit from allogeneic stem cell transplantation in first complete remission (CR1) has taken a step forward thanks to analysis of the UK NCRI AML17 and AML19 studies, reported at the 65th ASH Annual Meeting and Exposition. Patients who achieved molecular residual disease (MRD) negativity in their peripheral blood were at low risk of relapse, and had no benefit from allogeneic transplant in CR1, including those with the FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication mutation of the NPM1 (nucleophosmin 1) gene, that is generally considered to be a marker of poor risk. Peter Goodwin spoke with Jad Othman, MBBS, from King's College London and the Guy's and St Thomas' Hospital in London, and now based at the Royal North Shore Hospital in Sydney, Australia. Othman explained how testing for the FLT3 mutation of the NPM1 gene can be used along with assessment of molecular MRD to help choose patients who can benefit from transplant and spare those for whom the risk/benefit ratio is adverse.
In this episode, we dive into the management of newly diagnosed and relapsed FLT3-positive AML with Dr. Alexander Perl.Here are the shownotes:1. Assessment of minimal residual disease in standard-risk AML https://www.nejm.org/doi/full/10.1056/nejmoa1507471 2. RATIFY study: Midostaurin plus chemotherapy for AML with a FLT3 mutationhttps://www.nejm.org/doi/full/10.1056/nejmoa1614359 3. QuANTUM-First trial: Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trialhttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00464-6/fulltext 4. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groupshttps://ashpublications.org/blood/article/127/12/1551/35035/Benefit-of-high-dose-daunorubicin-in-AML-induction 5. Prospective Randomized Comparison of Idarubicin and High-Dose Daunorubicin in Induction Chemotherapy for Newly Diagnosed Acute Myeloid Leukemiahttps://ascopubs.org/doi/10.1200/JCO.2017.72.8618?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed 6. Phase 3 trial of gilteritinib plus azacitidine vs. azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapyhttps://ashpublications.org/blood/article/140/17/1845/486088/Phase-3-trial-of-gilteritinib-plus-azacitidine-vs 7. ADMIRAL: Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AMLhttps://www.nejm.org/doi/full/10.1056/nejmoa1902688 8. Venetoclax Plus Gilteritinib for FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemiahttps://ascopubs.org/doi/10.1200/JCO.22.00602?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed 9. Levis MJ, Hamadani M, Logan B, et al: BMT-CTN 1506 (MORPHO): A randomized trial of the FLT3 inhibitor gilteritinib as post-transplant maintenance for FLT3-ITD AML. EHA 2023 Hybrid Congress. Abstract LB2711. Presented June 11, 2023. 10. Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30455-1/fulltext?dgcid=raven_jbs_etoc_email
The treatment paradigm for the treatment of AML is changing. In this podcast, our faculty discuss quizartinib and the QuANTUM-First trial. Visit www.morningcommutepodcast.com/aml3 to view the activity and CME/CE information, download the transcript, and complete the post-test and evaluation to earn CME/CE credit.
FLT3-inhibitors, such as quizartinib, are changing the treatment paradigm for AML, in this podcast, our faculty take a look at the drug class, how they are used in AML, and how to manage any treatment-related adverse events. Visit www.morningcommutepodcast.com/aml4 to view the activity and CME/CE information, download the transcript, and complete the post-test and evaluation to earn CME/CE credit.
In this podcast our faculty discuss the latest treatment options for AML that target FLT3 mutations: midostaurin, gilteritinib, and the new kid on the block, quizartinib. Visit www.morningcommutepodcast.com/aml2 to view the activity and CME/CE information, download the transcript, and complete the post-test and evaluation to earn CME/CE credit.
Our faculty discuss the importance of biomarker testing for FLT3 and FLT3-ITD and the prognostic impact for these patients, especially now that there are therapies targeting these mutations. Visit www.morningcommutepodcast.com/aml1 to view the activity and CME/CE information, download the transcript, and complete the post-test and evaluation to earn CME/CE credit.
BUFFALO, NY- November 8, 2023 – A new editorial #paper was #published in Oncotarget's Volume 14 on March 31, 2023, entitled, “Impact of SHP2 tyrosine phosphorylation on the development of acquired resistance to allosteric SHP2 inhibitors.” The SH2 domain-containing tyrosine phosphatase 2 (SHP2) is a ubiquitously expressed non-receptor protein tyrosine phosphatase, encoded by the PTPN11 gene. It is positively regulated by upstream receptor tyrosine kinases (RTKs) to activate downstream the RAS-ERK pathway. In this new editorial, researchers Giulia Franciosa and Jesper V. Olsen from the University of Copenhagen discuss potential leukemia therapies that effectively prevent adaptive resistance. Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by a blockage of differentiation and an uncontrolled proliferation of myeloid hematopoietic progenitor cells. The internal tandem duplication (ITD) in the juxtamembrane domain of the RTK FLT3 is an oncogenic driver mutation that leads to constitutive activation of its tyrosine kinase activity. Consequently, FLT3 inhibitors that block its tyrosine kinase activity represent the targeted treatment option for patients with FLT3-ITD AML, often administrated in combination with induction chemotherapy. “Nevertheless, the short duration of remission urges the development of novel combinatorial therapies for FLT3-ITD AML.” Since 2016, several potent and selective allosteric, noncovalent SHP2 inhibitors have been developed and tested in clinical trials for solid tumors. A recent study reported the effectiveness of short-term treatment with the allosteric SHP2 inhibitor SHP099 as a single agent in clinically relevant mouse models of Flt3-ITD AML. This observation was in contrast with published data showing that allosteric SHP2 inhibition is only effective as combination treatment with inhibitors of other nodes of the RAS-ERK pathway. In a research article published by Pfeiffer et al., the Olsen's lab at University of Copenhagen showed that two commercial FLT3-ITDpositive AML cell lines (MV-4-11 and MOLM-13) developed adaptive resistance after prolonged treatment in vitro with the allosteric SHP2 inhibitor SHP099. “All in all, the findings by Pfeiffer et al. suggest that combined inhibition of SHP2 and mutated RTKs are effective in preventing adaptive resistance, but also highlight the need for development of more potent and effective SHP2 inhibitors and combination therapies for clinical applications.” DOI - https://doi.org/10.18632/oncotarget.28392 Correspondence to - Giulia Franciosa - giulia.franciosa@cpr.ku.dk Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28392 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, SHP2, PTPN11, tyrosine, phosphorylation About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
In the second portion of our two part-series on AML maintenance, Anthony and Bernie delve into the studies of post-transplant FLT3 inhibitor maintenance. We discuss the controversial MORPHO study of gilteritinib and whether these results will change practice! Sorafenib observational study: https://pubmed.ncbi.nlm.nih.gov/30809038/ SORMAIN (sorafenib): https://pubmed.ncbi.nlm.nih.gov/32673171/ Chinese Sorafenib Phase III: https://pubmed.ncbi.nlm.nih.gov/32791048/ RADIUS (midostaurin): https://pubmed.ncbi.nlm.nih.gov/33288862/ AMLSG 16-10 (midostaurin): https://pubmed.ncbi.nlm.nih.gov/30563875/ MORPHO (EHA abstract): https://library.ehaweb.org/eha/2023/eha2023-congress/391322/faculty.presenters.bmt-ctn.1506.28morpho29.a.randomized.trial.of.the.flt3.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dmorpho
Go online to PeerView.com/HGR860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In recent years, the “circle” of personalized disease management for acute myeloid leukemia (AML) has been expanded, and clinicians are now able to utilize innovative therapeutics, such as novel cytotoxic platforms, targeted agents, immunotherapy, and epigenetic approaches, that can be tailored to patients' diverse medical needs. This Clinical Consults activity pairs rapid-fire, case-based discussions with mini lecture sessions wherein the experts support their treatment recommendations by presenting the evidence that supports the use of cutting-edge therapeutics—including newer FLT3 inhibitors, chemo-free targeted platforms, epigenetic agents, and emerging antibody platforms —in various AML settings. Join the experts and learn how you can successfully “expand the circle” of personalized care in AML! Upon completion of this activity, participants should be better able to: Cite baseline factors such as age, comorbidities, functional status, and cytogenetic/mutational findings that can inform personalized treatment selection in AML; Describe evidence supporting the personalized use of newer cytotoxic platforms, targeted agents, immunotherapy, radioimmunoconjugates, and epigenetic strategies as upfront treatment, maintenance therapy, or in the management of R/R AML; Develop personalized team-based management protocols for AML that integrate newer treatment modalities based on the presence or absence of targetable mutations, functional status, treatment setting, or subtype; and Manage optimized dosing, response monitoring, and safety considerations when using modern therapeutic platforms in the AML setting.
Go online to PeerView.com/HGR860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In recent years, the “circle” of personalized disease management for acute myeloid leukemia (AML) has been expanded, and clinicians are now able to utilize innovative therapeutics, such as novel cytotoxic platforms, targeted agents, immunotherapy, and epigenetic approaches, that can be tailored to patients' diverse medical needs. This Clinical Consults activity pairs rapid-fire, case-based discussions with mini lecture sessions wherein the experts support their treatment recommendations by presenting the evidence that supports the use of cutting-edge therapeutics—including newer FLT3 inhibitors, chemo-free targeted platforms, epigenetic agents, and emerging antibody platforms —in various AML settings. Join the experts and learn how you can successfully “expand the circle” of personalized care in AML! Upon completion of this activity, participants should be better able to: Cite baseline factors such as age, comorbidities, functional status, and cytogenetic/mutational findings that can inform personalized treatment selection in AML; Describe evidence supporting the personalized use of newer cytotoxic platforms, targeted agents, immunotherapy, radioimmunoconjugates, and epigenetic strategies as upfront treatment, maintenance therapy, or in the management of R/R AML; Develop personalized team-based management protocols for AML that integrate newer treatment modalities based on the presence or absence of targetable mutations, functional status, treatment setting, or subtype; and Manage optimized dosing, response monitoring, and safety considerations when using modern therapeutic platforms in the AML setting.
Go online to PeerView.com/HGR860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In recent years, the “circle” of personalized disease management for acute myeloid leukemia (AML) has been expanded, and clinicians are now able to utilize innovative therapeutics, such as novel cytotoxic platforms, targeted agents, immunotherapy, and epigenetic approaches, that can be tailored to patients' diverse medical needs. This Clinical Consults activity pairs rapid-fire, case-based discussions with mini lecture sessions wherein the experts support their treatment recommendations by presenting the evidence that supports the use of cutting-edge therapeutics—including newer FLT3 inhibitors, chemo-free targeted platforms, epigenetic agents, and emerging antibody platforms —in various AML settings. Join the experts and learn how you can successfully “expand the circle” of personalized care in AML! Upon completion of this activity, participants should be better able to: Cite baseline factors such as age, comorbidities, functional status, and cytogenetic/mutational findings that can inform personalized treatment selection in AML; Describe evidence supporting the personalized use of newer cytotoxic platforms, targeted agents, immunotherapy, radioimmunoconjugates, and epigenetic strategies as upfront treatment, maintenance therapy, or in the management of R/R AML; Develop personalized team-based management protocols for AML that integrate newer treatment modalities based on the presence or absence of targetable mutations, functional status, treatment setting, or subtype; and Manage optimized dosing, response monitoring, and safety considerations when using modern therapeutic platforms in the AML setting.
Go online to PeerView.com/HGR860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In recent years, the “circle” of personalized disease management for acute myeloid leukemia (AML) has been expanded, and clinicians are now able to utilize innovative therapeutics, such as novel cytotoxic platforms, targeted agents, immunotherapy, and epigenetic approaches, that can be tailored to patients' diverse medical needs. This Clinical Consults activity pairs rapid-fire, case-based discussions with mini lecture sessions wherein the experts support their treatment recommendations by presenting the evidence that supports the use of cutting-edge therapeutics—including newer FLT3 inhibitors, chemo-free targeted platforms, epigenetic agents, and emerging antibody platforms —in various AML settings. Join the experts and learn how you can successfully “expand the circle” of personalized care in AML! Upon completion of this activity, participants should be better able to: Cite baseline factors such as age, comorbidities, functional status, and cytogenetic/mutational findings that can inform personalized treatment selection in AML; Describe evidence supporting the personalized use of newer cytotoxic platforms, targeted agents, immunotherapy, radioimmunoconjugates, and epigenetic strategies as upfront treatment, maintenance therapy, or in the management of R/R AML; Develop personalized team-based management protocols for AML that integrate newer treatment modalities based on the presence or absence of targetable mutations, functional status, treatment setting, or subtype; and Manage optimized dosing, response monitoring, and safety considerations when using modern therapeutic platforms in the AML setting.
Go online to PeerView.com/HGR860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In recent years, the “circle” of personalized disease management for acute myeloid leukemia (AML) has been expanded, and clinicians are now able to utilize innovative therapeutics, such as novel cytotoxic platforms, targeted agents, immunotherapy, and epigenetic approaches, that can be tailored to patients' diverse medical needs. This Clinical Consults activity pairs rapid-fire, case-based discussions with mini lecture sessions wherein the experts support their treatment recommendations by presenting the evidence that supports the use of cutting-edge therapeutics—including newer FLT3 inhibitors, chemo-free targeted platforms, epigenetic agents, and emerging antibody platforms —in various AML settings. Join the experts and learn how you can successfully “expand the circle” of personalized care in AML! Upon completion of this activity, participants should be better able to: Cite baseline factors such as age, comorbidities, functional status, and cytogenetic/mutational findings that can inform personalized treatment selection in AML; Describe evidence supporting the personalized use of newer cytotoxic platforms, targeted agents, immunotherapy, radioimmunoconjugates, and epigenetic strategies as upfront treatment, maintenance therapy, or in the management of R/R AML; Develop personalized team-based management protocols for AML that integrate newer treatment modalities based on the presence or absence of targetable mutations, functional status, treatment setting, or subtype; and Manage optimized dosing, response monitoring, and safety considerations when using modern therapeutic platforms in the AML setting.
Go online to PeerView.com/DDE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of acute myeloid leukemia (AML) subtypes have been driven by a modern understanding of their biology and heterogeneity, including the recognition of disease-defining FLT3 mutations. FLT3 inhibitors are a potent therapeutic option for the targeted management of this AML subtype, and rapidly emerging evidence on newer FLT3 agents is reshaping treatment protocols for upfront therapy and for post-transplant maintenance. Are you prepared to challenge and change conventional care for FLT3-mutated AML? Find out by accessing this activity, where a leading AML expert assesses new evidence presented at recent scientific congresses that supports the integration of newer FLT3 inhibitors into practice while reviewing standards for mutation testing, as well as safety similarities and differences among available FLT3 agents. Upon completion of this activity, participants should be better able to: Summarize current guidelines and updated evidence on FLT3 mutation testing in acute myeloid leukemia (AML) and the use of next-gen FLT3 inhibitor options in newly diagnosed and relapsed/refractory AML; Implement modern treatment plans that utilize FLT3 inhibitors as standard therapy for FLT3-mutated AML patients, including in combination with intensive chemotherapy for HCT candidates or as part of novel combinatorial regimens; and Address the unique suite of adverse events associated with the use of FLT3 inhibitors in AML.
Go online to PeerView.com/DDE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of acute myeloid leukemia (AML) subtypes have been driven by a modern understanding of their biology and heterogeneity, including the recognition of disease-defining FLT3 mutations. FLT3 inhibitors are a potent therapeutic option for the targeted management of this AML subtype, and rapidly emerging evidence on newer FLT3 agents is reshaping treatment protocols for upfront therapy and for post-transplant maintenance. Are you prepared to challenge and change conventional care for FLT3-mutated AML? Find out by accessing this activity, where a leading AML expert assesses new evidence presented at recent scientific congresses that supports the integration of newer FLT3 inhibitors into practice while reviewing standards for mutation testing, as well as safety similarities and differences among available FLT3 agents. Upon completion of this activity, participants should be better able to: Summarize current guidelines and updated evidence on FLT3 mutation testing in acute myeloid leukemia (AML) and the use of next-gen FLT3 inhibitor options in newly diagnosed and relapsed/refractory AML; Implement modern treatment plans that utilize FLT3 inhibitors as standard therapy for FLT3-mutated AML patients, including in combination with intensive chemotherapy for HCT candidates or as part of novel combinatorial regimens; and Address the unique suite of adverse events associated with the use of FLT3 inhibitors in AML.
Go online to PeerView.com/DDE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of acute myeloid leukemia (AML) subtypes have been driven by a modern understanding of their biology and heterogeneity, including the recognition of disease-defining FLT3 mutations. FLT3 inhibitors are a potent therapeutic option for the targeted management of this AML subtype, and rapidly emerging evidence on newer FLT3 agents is reshaping treatment protocols for upfront therapy and for post-transplant maintenance. Are you prepared to challenge and change conventional care for FLT3-mutated AML? Find out by accessing this activity, where a leading AML expert assesses new evidence presented at recent scientific congresses that supports the integration of newer FLT3 inhibitors into practice while reviewing standards for mutation testing, as well as safety similarities and differences among available FLT3 agents. Upon completion of this activity, participants should be better able to: Summarize current guidelines and updated evidence on FLT3 mutation testing in acute myeloid leukemia (AML) and the use of next-gen FLT3 inhibitor options in newly diagnosed and relapsed/refractory AML; Implement modern treatment plans that utilize FLT3 inhibitors as standard therapy for FLT3-mutated AML patients, including in combination with intensive chemotherapy for HCT candidates or as part of novel combinatorial regimens; and Address the unique suite of adverse events associated with the use of FLT3 inhibitors in AML.
Go online to PeerView.com/DDE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of acute myeloid leukemia (AML) subtypes have been driven by a modern understanding of their biology and heterogeneity, including the recognition of disease-defining FLT3 mutations. FLT3 inhibitors are a potent therapeutic option for the targeted management of this AML subtype, and rapidly emerging evidence on newer FLT3 agents is reshaping treatment protocols for upfront therapy and for post-transplant maintenance. Are you prepared to challenge and change conventional care for FLT3-mutated AML? Find out by accessing this activity, where a leading AML expert assesses new evidence presented at recent scientific congresses that supports the integration of newer FLT3 inhibitors into practice while reviewing standards for mutation testing, as well as safety similarities and differences among available FLT3 agents. Upon completion of this activity, participants should be better able to: Summarize current guidelines and updated evidence on FLT3 mutation testing in acute myeloid leukemia (AML) and the use of next-gen FLT3 inhibitor options in newly diagnosed and relapsed/refractory AML; Implement modern treatment plans that utilize FLT3 inhibitors as standard therapy for FLT3-mutated AML patients, including in combination with intensive chemotherapy for HCT candidates or as part of novel combinatorial regimens; and Address the unique suite of adverse events associated with the use of FLT3 inhibitors in AML.
Go online to PeerView.com/DDE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Advances in the management of acute myeloid leukemia (AML) subtypes have been driven by a modern understanding of their biology and heterogeneity, including the recognition of disease-defining FLT3 mutations. FLT3 inhibitors are a potent therapeutic option for the targeted management of this AML subtype, and rapidly emerging evidence on newer FLT3 agents is reshaping treatment protocols for upfront therapy and for post-transplant maintenance. Are you prepared to challenge and change conventional care for FLT3-mutated AML? Find out by accessing this activity, where a leading AML expert assesses new evidence presented at recent scientific congresses that supports the integration of newer FLT3 inhibitors into practice while reviewing standards for mutation testing, as well as safety similarities and differences among available FLT3 agents. Upon completion of this activity, participants should be better able to: Summarize current guidelines and updated evidence on FLT3 mutation testing in acute myeloid leukemia (AML) and the use of next-gen FLT3 inhibitor options in newly diagnosed and relapsed/refractory AML; Implement modern treatment plans that utilize FLT3 inhibitors as standard therapy for FLT3-mutated AML patients, including in combination with intensive chemotherapy for HCT candidates or as part of novel combinatorial regimens; and Address the unique suite of adverse events associated with the use of FLT3 inhibitors in AML.
In this week's New FDA Approval's podcast episode, Dr. Emma Hitt Nichols discusses the latest FDA approvals from July 17, 2023 – July 21, 2023. Please check back every Monday morning so that you can stay up to date. Here are the highlights: Vanflyta® for FLT3-ITD+ AML The FDA has approved Vanflyta (quizartinib), developed by Daiichi Sankyo, for treating adult patients with acute myeloid leukemia (AML) having the FLT3-ITD mutation. The approval came after data from the QuANTUM-First trial showed improved overall survival rates when Vanflyta was added to treatment. This makes Vanflyta the third drug approved for FLT3-positive AML, joining Novartis' Rydapt® and Astellas Pharma's Xospata®. BeyfortusTM for RSV AstraZeneca's BeyfortusTM (nirsevimab) has been approved by the FDA for preventing respiratory syncytial virus (RSV) lower respiratory tract disease in neonates, infants, and children up to 24 months of age. The approval was supported by data from three clinical trials, and the drug has also been given a fast-track designation. Beyfortus becomes the second antibody available for RSV protection in young children, following palivizumab or Synagis®. Cyfendus Anthrax Vaccine The FDA has approved CyfendusTM (Anthrax Vaccine Adsorbed, Adjuvanted) for post-exposure prophylaxis following exposure to Bacillus anthracis, the bacterium causing Anthrax, in adults aged 18 to 65. The vaccine is administered in two doses, two weeks apart, and clinical trials have found it to be non-inferior to the already available BioThrax® vaccine. Cyfendus has been in use since 2019 under a pre-emergency use authorization. YcanthTM for Molluscum Contagiosum The FDA has approved Verrica Pharmaceuticals' YcanthTM (cantharidin) topical solution for treating molluscum contagiosum in patients aged 2 and older. The approval is based on results from two identical phase 3 trials involving over 500 patients. Despite being available via compounding sources for years, Ycanth is the first FDA-approved standardized product for molluscum contagiosum. This podcast is brought to you by Nascent Medical. If you're a project manager at a CME or medical communications agency and need on-call medical writing assistance please visit Nascent Medical. We are a team of MD- and PhD-level medical writers and can create slide decks, white papers, ad board summaries, manuscripts, needs assessments, and much more. We also do medical editing using AMA style and factchecking. Visit Nascent Medical. Intro and outro music Garden Of Love by Pk jazz Collective
PeerView Family Medicine & General Practice CME/CNE/CPE Video Podcast
Go online to PeerView.com/PYA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Newer treatment modalities for acute myeloid leukemia (AML) have rapidly eclipsed the decades-long cytarabine-based standard of care and helped clinicians adopt more personalized management using innovative cytotoxic platforms, targeted agents (including FLT3, BCL2, and IDH inhibitors), and other unique management strategies. Clinicians can now improve patient outcomes across all AML treatment settings, while at the same time selecting the most potent, personalized option that can be designed to address a given patient's needs. This “Seminars and Tumor Board” activity, adapted from our recent live event held at the 2023 ASCO Annual Meeting and developed in collaboration with the HealthTree Foundation for Acute Myeloid Leukemia, reveals how modern baseline assessment paired with cutting-edge prognostication has pushed patient management to new heights of innovation and changed the management of patients with AML with therapeutically relevant features (such as FLT3 or IDH mutations), patients presenting without driver mutations, or individuals with comorbid illnesses or higher-risk features. Join the AML experts for a real-world “Tumor Board”–style discussion of how the latest evidence can inform your practice. Upon completion of this activity, participants should be better able to: Summarize baseline patient-related and disease-related factors, including age, comorbidities, functional status, and cytogenetic/mutational findings, that can influence prognostication and treatment selection in AML; Cite current evidence supporting the personalized use of novel treatment modalities, including new cytotoxic platforms, targeted agents, immunotherapy, and epigenetic strategies, for the management of newly diagnosed or relapsed/refractory AML; Integrate novel therapeutics into the personalized team-based management of AML according to the results of baseline assessment, presence or absence of targetable mutations, functional status, or AML subtype; and Address care delivery considerations, including optimized dosing and safety management, when caring for patients with AML
Go online to PeerView.com/PYA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Newer treatment modalities for acute myeloid leukemia (AML) have rapidly eclipsed the decades-long cytarabine-based standard of care and helped clinicians adopt more personalized management using innovative cytotoxic platforms, targeted agents (including FLT3, BCL2, and IDH inhibitors), and other unique management strategies. Clinicians can now improve patient outcomes across all AML treatment settings, while at the same time selecting the most potent, personalized option that can be designed to address a given patient's needs. This “Seminars and Tumor Board” activity, adapted from our recent live event held at the 2023 ASCO Annual Meeting and developed in collaboration with the HealthTree Foundation for Acute Myeloid Leukemia, reveals how modern baseline assessment paired with cutting-edge prognostication has pushed patient management to new heights of innovation and changed the management of patients with AML with therapeutically relevant features (such as FLT3 or IDH mutations), patients presenting without driver mutations, or individuals with comorbid illnesses or higher-risk features. Join the AML experts for a real-world “Tumor Board”–style discussion of how the latest evidence can inform your practice. Upon completion of this activity, participants should be better able to: Summarize baseline patient-related and disease-related factors, including age, comorbidities, functional status, and cytogenetic/mutational findings, that can influence prognostication and treatment selection in AML; Cite current evidence supporting the personalized use of novel treatment modalities, including new cytotoxic platforms, targeted agents, immunotherapy, and epigenetic strategies, for the management of newly diagnosed or relapsed/refractory AML; Integrate novel therapeutics into the personalized team-based management of AML according to the results of baseline assessment, presence or absence of targetable mutations, functional status, or AML subtype; and Address care delivery considerations, including optimized dosing and safety management, when caring for patients with AML
Go online to PeerView.com/PYA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Newer treatment modalities for acute myeloid leukemia (AML) have rapidly eclipsed the decades-long cytarabine-based standard of care and helped clinicians adopt more personalized management using innovative cytotoxic platforms, targeted agents (including FLT3, BCL2, and IDH inhibitors), and other unique management strategies. Clinicians can now improve patient outcomes across all AML treatment settings, while at the same time selecting the most potent, personalized option that can be designed to address a given patient's needs. This “Seminars and Tumor Board” activity, adapted from our recent live event held at the 2023 ASCO Annual Meeting and developed in collaboration with the HealthTree Foundation for Acute Myeloid Leukemia, reveals how modern baseline assessment paired with cutting-edge prognostication has pushed patient management to new heights of innovation and changed the management of patients with AML with therapeutically relevant features (such as FLT3 or IDH mutations), patients presenting without driver mutations, or individuals with comorbid illnesses or higher-risk features. Join the AML experts for a real-world “Tumor Board”–style discussion of how the latest evidence can inform your practice. Upon completion of this activity, participants should be better able to: Summarize baseline patient-related and disease-related factors, including age, comorbidities, functional status, and cytogenetic/mutational findings, that can influence prognostication and treatment selection in AML; Cite current evidence supporting the personalized use of novel treatment modalities, including new cytotoxic platforms, targeted agents, immunotherapy, and epigenetic strategies, for the management of newly diagnosed or relapsed/refractory AML; Integrate novel therapeutics into the personalized team-based management of AML according to the results of baseline assessment, presence or absence of targetable mutations, functional status, or AML subtype; and Address care delivery considerations, including optimized dosing and safety management, when caring for patients with AML
Go online to PeerView.com/PYA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Newer treatment modalities for acute myeloid leukemia (AML) have rapidly eclipsed the decades-long cytarabine-based standard of care and helped clinicians adopt more personalized management using innovative cytotoxic platforms, targeted agents (including FLT3, BCL2, and IDH inhibitors), and other unique management strategies. Clinicians can now improve patient outcomes across all AML treatment settings, while at the same time selecting the most potent, personalized option that can be designed to address a given patient's needs. This “Seminars and Tumor Board” activity, adapted from our recent live event held at the 2023 ASCO Annual Meeting and developed in collaboration with the HealthTree Foundation for Acute Myeloid Leukemia, reveals how modern baseline assessment paired with cutting-edge prognostication has pushed patient management to new heights of innovation and changed the management of patients with AML with therapeutically relevant features (such as FLT3 or IDH mutations), patients presenting without driver mutations, or individuals with comorbid illnesses or higher-risk features. Join the AML experts for a real-world “Tumor Board”–style discussion of how the latest evidence can inform your practice. Upon completion of this activity, participants should be better able to: Summarize baseline patient-related and disease-related factors, including age, comorbidities, functional status, and cytogenetic/mutational findings, that can influence prognostication and treatment selection in AML; Cite current evidence supporting the personalized use of novel treatment modalities, including new cytotoxic platforms, targeted agents, immunotherapy, and epigenetic strategies, for the management of newly diagnosed or relapsed/refractory AML; Integrate novel therapeutics into the personalized team-based management of AML according to the results of baseline assessment, presence or absence of targetable mutations, functional status, or AML subtype; and Address care delivery considerations, including optimized dosing and safety management, when caring for patients with AML
Go online to PeerView.com/PYA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Newer treatment modalities for acute myeloid leukemia (AML) have rapidly eclipsed the decades-long cytarabine-based standard of care and helped clinicians adopt more personalized management using innovative cytotoxic platforms, targeted agents (including FLT3, BCL2, and IDH inhibitors), and other unique management strategies. Clinicians can now improve patient outcomes across all AML treatment settings, while at the same time selecting the most potent, personalized option that can be designed to address a given patient's needs. This “Seminars and Tumor Board” activity, adapted from our recent live event held at the 2023 ASCO Annual Meeting and developed in collaboration with the HealthTree Foundation for Acute Myeloid Leukemia, reveals how modern baseline assessment paired with cutting-edge prognostication has pushed patient management to new heights of innovation and changed the management of patients with AML with therapeutically relevant features (such as FLT3 or IDH mutations), patients presenting without driver mutations, or individuals with comorbid illnesses or higher-risk features. Join the AML experts for a real-world “Tumor Board”–style discussion of how the latest evidence can inform your practice. Upon completion of this activity, participants should be better able to: Summarize baseline patient-related and disease-related factors, including age, comorbidities, functional status, and cytogenetic/mutational findings, that can influence prognostication and treatment selection in AML; Cite current evidence supporting the personalized use of novel treatment modalities, including new cytotoxic platforms, targeted agents, immunotherapy, and epigenetic strategies, for the management of newly diagnosed or relapsed/refractory AML; Integrate novel therapeutics into the personalized team-based management of AML according to the results of baseline assessment, presence or absence of targetable mutations, functional status, or AML subtype; and Address care delivery considerations, including optimized dosing and safety management, when caring for patients with AML
Go online to PeerView.com/PYA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Newer treatment modalities for acute myeloid leukemia (AML) have rapidly eclipsed the decades-long cytarabine-based standard of care and helped clinicians adopt more personalized management using innovative cytotoxic platforms, targeted agents (including FLT3, BCL2, and IDH inhibitors), and other unique management strategies. Clinicians can now improve patient outcomes across all AML treatment settings, while at the same time selecting the most potent, personalized option that can be designed to address a given patient's needs. This “Seminars and Tumor Board” activity, adapted from our recent live event held at the 2023 ASCO Annual Meeting and developed in collaboration with the HealthTree Foundation for Acute Myeloid Leukemia, reveals how modern baseline assessment paired with cutting-edge prognostication has pushed patient management to new heights of innovation and changed the management of patients with AML with therapeutically relevant features (such as FLT3 or IDH mutations), patients presenting without driver mutations, or individuals with comorbid illnesses or higher-risk features. Join the AML experts for a real-world “Tumor Board”–style discussion of how the latest evidence can inform your practice. Upon completion of this activity, participants should be better able to: Summarize baseline patient-related and disease-related factors, including age, comorbidities, functional status, and cytogenetic/mutational findings, that can influence prognostication and treatment selection in AML; Cite current evidence supporting the personalized use of novel treatment modalities, including new cytotoxic platforms, targeted agents, immunotherapy, and epigenetic strategies, for the management of newly diagnosed or relapsed/refractory AML; Integrate novel therapeutics into the personalized team-based management of AML according to the results of baseline assessment, presence or absence of targetable mutations, functional status, or AML subtype; and Address care delivery considerations, including optimized dosing and safety management, when caring for patients with AML
Do you understand the role of non-targetable driver mutations in the management of acute myeloid leukemia (AML)? Credit available for this activity expires: 5/1/2024 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/991353?ecd=bdc_podcast_libsyn_mscpedu
Go online to PeerView.com/GFT860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Oncology nurse professionals play a particularly important role in providing high-quality and increasingly personalized care to patients with acute myeloid leukemia (AML)—but how current are you with the “real-world” practice of nursing care in AML? Find out in this activity, featuring an oncology nurse's expert overview of nursing principles that can be used to modernize care and optimize the use of innovative targeted therapies (such as FLT3, IDH1/2, and BCL-2 inhibitors) across the treatment continuum. Upon completion of this activity, participants should be better able to: Recognize clinical symptoms, patient-related factors, and molecular/genetic features that influence AML treatment decisions and prognosis; Summarize efficacy and safety evidence related to novel targeted and epigenetic options for the management of newly diagnosed AML, postremission disease, and the relapsed/refractory setting; Educate patients with AML about therapeutic choices with novel agent classes, treatment expectations, dosing and adherence, and safety considerations; and Manage adverse events experienced by patients with AML receiving novel targeted and epigenetic options as part of their care.
Go online to PeerView.com/XSA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Are you ready to leverage the benefits of the wide range of newly approved therapeutics that are revolutionizing patient care in AML? Find out in this “Clinical Consults” activity based on a recording at the 2023 USCAP Annual Meeting. A pathologist and a hematologist-oncologist team up to discuss how modern diagnostic techniques can lead to better, more collaborative, personalized care using novel therapeutics to manage challenging AML cases (including in high-risk and mutation-defined AML) and use cases to illustrate diagnostic testing techniques and how pathology and hem-onc can collaborate on treatment decision-making. Watch this video activity today and hear how pathologists and hematologist-oncologists can team up for better outcomes! Upon completion of this activity, participants should be better able to: Discuss the cytogenetic and histopathologic features that enable diagnosis and influence prognosis of different AML subtypes, including secondary AML/AML-MRC or FLT3, IDH1/2, or TP53-mutated disease; Select appropriate molecular/pathology tests to establish a diagnosis of AML or a specific AML subtype and collect relevant information for subsequent treatment decisions; Summarize current evidence supporting innovative cytotoxic, targeted, and immunotherapy strategies in different AML subtypes, including high-risk and mutation-defined disease; and Facilitate the integration of novel therapeutics into team treatment plans informed by baseline test results, including for patients with secondary AML/AML-MRC or FLT3, IDH1/2, or TP53-mutated AML.
Featuring perspectives from Dr Richard Stone, including the following topics: Current and future trends in the care of patients with acute myeloid leukemia (AML) (0:00) Management of AML with IDH1/2 and FLT3 mutations (17:28) Advances in the treatment of high-risk AML (29:42) Emerging data with novel therapies for AML with targetable mutations (36:53) Hematopoietic stem cell transplantation as a treatment option for patients with relapsed or refractory AML (51:15) Advances in the care of patients with myelodysplastic syndromes (56:19) CME information and select publications
Study showing the time from diagnosis of AML to the start of intensive treatment indicate that a treatment delay has no negative prognostic impact. https://ashpublications.org/blood/article/136/7/823/460669/Does-time-from-diagnosis-to-treatment-affect-the RATIFY clinical trial showing the addition of midostaurin (FLT3 inhibitor) to 7+3 chemotherapy for AML https://www.nejm.org/doi/full/10.1056/nejmoa1614359 Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the European LeukemiaNet (ELN) https://ashpublications.org/blood/article/140/12/1345/485817/Diagnosis-and-management-of-AML-in-adults-2022 ASH 2022 abstract presenting Daunorubicin 60 Vs 90 mg/m2 https://ash.confex.com/ash/2022/webprogram/Paper157126.html ALFA-0701. The addition of gemtuzumab ozogamicin, an anti-CD33 antibody conjugate, to the standard treatment for patients with acute myeloid leukemiahttps://www.thelancet.com/article/S0140-6736(12)60485-1/fulltext Quizartinib data presented at EHA 2022 https://library.ehaweb.org/eha/2022/eha2022-congress/356965/harry.erba.quizartinib.prolonged.survival.vs.placebo.plus.intensive.induction.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2233%2Amarker%3D1749%2Afeatured%3D17676 International Consensus Classification (ICC) of Myeloid Neoplasms and Acute Leukemiashttps://ashpublications.org/blood/article/140/11/1200/485730/International-Consensus-Classification-of-Myeloid The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasmshttps://www.nature.com/articles/s41375-022-01613-1 CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemiahttps://ascopubs.org/doi/10.1200/JCO.2017.77.6112?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remissionhttps://www.nejm.org/doi/full/10.1056/NEJMoa2004444