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ASH 2024 | Key knowledge gaps in frontline AML: improving CR rates and combinations with targeted agents
Ioannis Mantzaris, MD, Montefiore Medical Center/Albert Einstein College of Medicine, New York City, NY, highlights the key knowledge gaps in the treatment of frontline acute myeloid leukemia (AML). He specifically mentions improving the rates of complete remission (CR), which currently stand at 60-70% with the 7+3 regimen. Dr Mantzaris notes that the addition of targeted agents has led to more individualized treatment approaches, but the integration of these agents with intensive chemotherapy remains a topic of research. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (AI-generated)
So, kind of alluded to it, you know, 7+3, again, one of the most widely used regimens for upfront therapy in the fit population of acute myeloid leukemia patients newly diagnosed. It does produce an acceptable rate of complete remissions, but that rate is like 60 to 70 percent, grossly speaking for all comers. When you look at the quality of those responses by MRD, they tend to be in the 30-40% range...
So, kind of alluded to it, you know, 7+3, again, one of the most widely used regimens for upfront therapy in the fit population of acute myeloid leukemia patients newly diagnosed. It does produce an acceptable rate of complete remissions, but that rate is like 60 to 70 percent, grossly speaking for all comers. When you look at the quality of those responses by MRD, they tend to be in the 30-40% range. So I guess the gap is how can we improve upon that? And that was, I guess, the impetus for our trial to combine a different agent that has shown so much promise in the older population of AML patients. Can we combine venetoclax that showed that promise with intensive chemotherapy and take those numbers that 7+3 has been historically producing and make them higher. Obviously, before we looked at that, we want to make sure that the combination is safe. So that’s why we did a dose escalation trial to assess safety first and then look at the signal of efficacy. So I guess the main gap when we looked at upfront AML therapy for most patients is a lack of knowledge of how we improve the rates of CR. Now obviously over the last few years, there’s been the addition of additional agents in the treatment armamentarium for newly diagnosed AML and the process has been a little bit more individualized based on the molecular profile of the patients. We have upfront therapies for FLT3 ITD mutated or FLT3 mutated in general patients with AML where we use FLT3 inhibitors, for example. We have gemtuzumab ozogamicin for particularly core-binding factor in acute myeloid leukemia patients. We now see the merging of other targeted agents for KMT2A rearranged and NPM1 mutated AML such as menin inhibitors that are being a very hot topic and a very promising class of agents these days. How our results are going to, how do we reconcile our results with the addition of novel agents? It’s, I think, the question for the future.
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