Dr Daver on the Efficacy of Revumenib in NPM1+ Relapsed/Refractory AML

“We showed in a pretty big population that there was no difference in terms of survival in [patients] with relapsed NPM1 mutation [who received second] salvage and [third] salvage [therapies], and the median survival is about 6 to 7 months.”

Naval G. Daver, MD, a professor and director of the Leukemia Research Alliance Program in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, highlighted the efficacy of menin inhibitor revumenib (Revuforj) in the treatment of patients with NPM1-mutant, relapsed/refractory acute myeloid leukemia (AML).

Outcomes between patients with relapsed/refractory AML can vary, and NMP1 mutations have been associated with poorer outcomes, Daver began. Data from the phase 2 portion of the AUGMENT-101 trial (NCT04065399) revealed that there were no survival differences in patients with NMP1-mutant, relapsed/refractory disease who had received second salvage or third salvage therapies, he explained. Therefore, there is a significant unmet need for patients with NMP1-mutant relapsed/refractory AML.

The study evaluated revumenib in patients with relapsed/refractory AML who harbor MLL/KMT2A gene rearrangements or NPM1 mutations. In the phase 2 portion of the study, patients with NPM1 mutations (n = 84) experienced a complete remission (CR) and CR with partial hematologic recovery (CRh) rate of 23.4%. (1-sided P = .0014); the median duration of CR/CRh was 4.7 months. Of note, the overall response rate (ORR) was 46.9%.

Historically, CR/CRh rates have been approximately 10% to 15% in this setting, with ORRs approximately less than 30% to 35%, meaning that revumenib may provide an improvement in these areas, Daver emphasized. However, a maximum benefit with this agent and other menin inhibitors may be seen as these treatments move to the up-front combinations or in salvage combinations, he concluded.

Notably, in November 2024, the FDA approved revumenib for the treatment of adult or pediatric patients at least 1 year of age or older with relapsed/refractory AML who harbor KMT2A translocation. This regulatory decision was supported by data from AUGMENT-101 trial.