In older patients with newly diagnosed NPM1-mutated (NPM1m) or KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML), adding revumenib to an azacitidine plus venetoclax regimen yields promising response results. This is according to interim results from a phase Ib dose-escalation sub-study presented at the European Hematology Association 2024 Hybrid Congress in Madrid, Spain.
“Revumenib is an oral menin inhibitor studied as a single agent in relapsed/refractory NPM1m or KMT2Ar AML with an overall response rate of 53%,” the sub-study authors noted regarding the agent.
The sub-study was a part of the Beat AML Master Trial and involved patients aged 60 years or older with newly diagnosed NPM1m or KMT2Ar AML. It sought to determine the recommended dose for adding revumenib to azacitidine plus venetoclax in this population.
The cohort of 13 patients received azacitidine at 75 mg/m2 for the first seven days of the study and venetoclax as a 400 mg dose-adjusted for first 28 days. These patients were divided into two revumenib dosing cohorts.
From days one to 28 of the study, seven patients received oral revumenib at 113 mg every 12 hours, among whom only one patient experienced hematologic dose-limiting toxicity (DLT). Six patients received the agent at 163 mg every 12 hours, and none experienced DLT.
Regarding adverse events experienced in the total cohort, QTcF prolongation occurred in 38% of patients and differentiation syndrome in 31%, but there were few cases of treatment-related grade 3 toxicity.
The total cohort had a composite complete remission rate of 100%. The researchers added that “[o]f the 12 patients tested by centralized flow cytometry (sensitivity of .01%) none had measurable residual disease.”
The median follow-up of the patients was 7.6 months. Five of the 13 patients are still in the study. Four patients discontinued treatment due to adverse events, two others due to relapse, and two due to allogeneic stem cell transplant. There were two patient mortalities following treatment discontinuation.
Reference
Zeidner J, Lin TL, Welkie R, et al. Phase 1B study of azacitidine, venetoclax and revumenib in newly diagnosed older adults with NPM1 mutated or KMT2A rearranged AML: Interim results of dose escalation from the Beat AML Consortium. Abstract #S134. Presented at the European Hematology Association 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain.