Real‑World Results for Menin Inhibitors in Hard‑to‑Treat AML | Kuo-Kai Chin, MD

My name is Kuo-Kai Chin, and I'm an assistant attending Memorial Sloan-Kettering Cancer Center.

I just presented data on outcomes of patients with relapsed or refractory acute myeloid leukemia after the use of menin inhibitors.

Menin inhibitors are a very exciting new class of drugs that are currently being developed and used in patients with acute myeloid leukemia, specifically, patients with mutations in NPM1 and KMT2A.

Very common mutations in acute myeloid leukemia are eligible to get this treatment. It's actually FDA approved in patients who have relapsed or refractory AML in the United States.

The two menin inhibitors that you might have heard of, our revumenib and ziftomenib, and they're both approved for relapsed or refractory AML patients with the correct mutations.

What my studies and my research looks at is what happens to patients who have tried these inhibitors and unfortunately, either had them not work or have them stop working and therefore relapse after a response.

My studies have shown with my group that the outcomes for these patients are unfortunately poor and patients live on average about four months if these treatments stop working.

However, we also show that it is possible to go back into remission with subsequent treatments after the failure of these menin inhibitors. Specifically, we thought we saw that patients who received treatments that contained the targeted drug Venetoclax, are most likely to go into remission after menin inhibitor stopped working.

The studies are very early and the sample size is relatively small, but we think that is one possible promising approach.

Another promising approach that we're looking at is the rotation of menin inhibitors. In our study, we show a few cases of patients who got one menin inhibitor, switched to another one and were able to get back into remission.

This is a really potentially exciting and promising approach that we think deserves more studies because, knowing whether or not you can get back into remission by switching menin inhibitors will have huge implications for patients who are faced with this dilemma in the future.

In addition, we also think this topic will also become increasingly important because menin inhibitors are being used in additional context and combinations.

There are many exciting studies that are now looking at menin inhibitors. For patients with newly diagnosed acute myeloid leukemia that have the relevant mutations. If those studies are positive, many patients will become menin exposed, so to speak, and might need options for salvage later after a menin inhibitor.

So in summary, outcomes currently in patients who have had a menin inhibitor and either did not respond or relapsed afterwards, or are relatively poor with a limited overall survival.

However, there is the possibility of re-achieving a remission with certain specific strategies.

Venetoclax based strategies seem promising at this moment, and there's also the possibility that switching menin inhibitors might also get patients back into remission.

We hope that additional studies will focus on both the optimal sequencing of treatments, the possibility of overcoming menin inhibitor resistance, and therefore lead to better outcomes for all patients with acute myeloid leukemia.

Thank you.

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