The Role of Menin Inhibitors in the AML Treatment Armamentarium

EP: 1.The Role of Molecular Testing in Diagnosing Acute Myeloid Leukemia

EP: 2.When to Perform Molecular Testing in Relapsed AML

EP: 3.Barriers to Molecular Testing in AML

EP: 4.Treating Newly Diagnosed Acute Myeloid Leukemia

EP: 5.Treatment Options for a Young, Fit Patient Newly Diagnosed with AML

EP: 6.First-Line Treatment Options for NPM1-mutant AML

EP: 7.First-Line Treatment Options for AML With KMT2a Rearrangements

EP: 8.The Potential Role of Menin Inhibitors in the Front-Line Treatment of AML

EP: 9.Exploring Potential Combination Treatments for AML

EP: 10.Menin Inhibitors in the Second-Line Treatment of AML

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EP: 11.The Role of Menin Inhibitors in the AML Treatment Armamentarium

EP: 12.Determining Which Patients Will Benefit the Most From Menin Inhibitor Treatment

EP: 13.The AML Treatment Horizon

EP: 14.Menin Inhibitors in Acute Myeloid Leukemia: An Overview of “Encouraging” Early Data

Transcript:

Naval G. Daver, MD: Maybe [we can talk] a little bit more about resistance mutations. [Dr Pollyea], have you had much experience with the menin inhibitors and how do you think that these could be moved forward? Should we be looking to combine them? What are the combination partners you can think of: venetoclax, FLT3 [inhibitors], chemo[therapy]? What would be the first shot you would like to go with these menin inhibitors?

Daniel Pollyea, MD, MS: Thanks. I’ve had more limited experience than you all, but dipping our toes in the water and finding it fascinating, particularly the Nature paper you referenced. It’s quite an accomplishment for a phase 1 study to have clinical and translational data come out in Nature, just really remarkable and shouldn’t be surprising in our field. This is sort of what we’ve come to expect, but really amazing work by our colleagues. I’m excited about the opportunity to pair this with up-front regimens. And I gave my thoughts before about how it may or may not pair well with a venetoclax-based regimen, but this is a situation that I do think would potentially have some additive properties with an intensive induction regimen. It’s also, biologically or demographically, I should say, it’s a bit more common in younger patients in our field. And those patients are often more able to tolerate an intensive chemotherapy regimen. So I’m excited about that combination in the near future to see how that might work, what the tolerability profile is, etc.

The other potentially advantageous rationale for an up-front combination with chemotherapy would be the differentiation syndrome that we’ve heard about. It may be a way to mitigate that because the chemotherapeutic agents might be able to cytoreduce a lot of the disease that is causing all the chaos with respect to the differentiation, so another reason to perhaps be excited about that. And then the third thing I’ll mention that I don’t think it has come up yet this morning in our discussion is the unbelievable MRD [minimum residual disease] clearance that we’re seeing with all these therapies that have been reported so far. Say what you want about response rates and how can we get better. We all know we want to or need to. As [Dr Erba] said, there’s precedence in our field for single-targeted therapies to get approved with similar response rates to what we’ve seen. But regardless, we have not seen targeted therapies such as these get MRD negativity with what’s being reported. It’s really incredible. I would say that that’s not something we’ve seen with FLT3 inhibitors or IDH inhibitors, so I’m really excited about that. I think it gives another sort of rationale for perhaps being a therapy that plays well with others in the up-front setting. We talk about this all the time with other drugs, but there may be a role for this therapy to deepen remissions or to get MRD to clear post treatment or post transplant. I think these are other opportunities we can think about.

Transcript is edited for clarity and readability.