ASH 2025 | Systematic review and meta-analysis of menin inhibitors for the treatment of AML

This is a project that one of our residents here at Yale presented and is leading. And this is a systematic review and meta-analysis of prior studies that evaluated a new class of targeted therapies in AML patients. And those medications are known as menin inhibitors. And there are different compounds that have been developed by various pharmaceutical companies. Two of them have already been approved by the FDA for the treatment of patients with either NPM1 mutations or KMT2A rearrangements. So this is an emerging class of agents that is now already in clinical practice. However, the efficacy and safety profile of those different menin inhibitors, either as monotherapy or in combination therapy for adult patients with AML is unknown. And there’s no head-to-head comparison, which is the best and safest menin inhibitor. So we performed a systematic review and meta-analysis of various different databases and looked at studies that reported outcomes for patients with acute myeloid leukemia who were treated with menin inhibitors in both the relapsed/refractory setting as well as frontline. And so we found 488 articles in the initial search and ultimately ended up including nine in our study. And those nine articles included around 550 patients. And we could see that there was a pooled overall response rate of 59.7% with slightly higher responses for patients with NPM1 mutant disease versus KMT2A rearrangement, although that was just numerically higher, but not statistically significant. We also then looked at different combination therapies of menin inhibitors with either venetoclax or azacitidine or intensive chemotherapy and did see similar findings here. Yeah, and then lastly, we also looked at the pooled adverse event profile and it’s largely in line with what we would see with the individual agents in clinical trials, meaning nausea and diarrhea as well as febrile neutropenia were the most commonly reported adverse events. And then notable side effects of this class of agents is differentiation syndrome as well as QTc prolongation. And those were reported in 18.6 and 9.1% of patients respectively. So we’re currently in the process of updating this analysis based on several really exciting studies that were presented at ASH this year. And I hope this will then enable us to at least have some indirect comparison of what could be the best menin inhibitor. However, I do think menin inhibitors in general are a valuable addition to our treatment options for patients. And I’m just excited that this is now available for patients.

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