Multicenter phase 1 trial of first-line azacitidine, venetoclax, and revumenib for NPM1-mutated or KMT2A-rearranged AML

Azacitidine and venetoclax is a standard frontline treatment for AML in older adults; however, long-term outcomes remain poor. A multicenter phase 1-trial in the USA evaluated the first-line combination of azacitidine, venetoclax and the oral menin inhibitor revumenib for AML with nucleophosmin-1 mutation (NPM1m) or lysine methyltransferase 2a rearrangement (KMT2Ar) in patients aged 60 years or older. The combination was well tolerated, without an identified maximal tolerated dose, and had encouraging activity. The median time to first response was 28 days. All 37 patiens evaluated had no evidence of measurable residual disease. The authors conclude that in older adults with newly diagnosed NMP1m or KMT2Ar AML, the combination of azacitidine, venetoclax, and revumenib was safe and had high rates of clinical activity.