Abstract

Summary Acute myeloid leukaemia (AML) arising from a myeloproliferative neoplasm (MPN) is more aggressive and less responsive to therapies compared to de novo AML. Olutasidenib, an oral small‐molecule inhibitor of mutated IDH1 (mIDH1), showed encouraging and durable responses in a phase 1/2 study of adults with post‐MPN m IDH1 AML. Patients received olutasidenib 150 mg BID monotherapy or in combination with azacitidine. Primary end‐points: safety and best response defined as complete remission (CR), CR with partial haematological recovery or morphological leukaemia‐free state (MLFS). Analysis included 15 patients with post‐MPN m IDH1 AML; 10 had relapsed or refractory AML and five had newly diagnosed AML. Six were treated with olutasidenib monotherapy and nine in combination with azacitidine. Treatment emergent adverse events occurred in 15 patients, three of whom discontinued therapy. CR: 40% ( n = 6/15); median duration of response: 15.6 months (range: 1.7–44.3); CR with incomplete haematological recovery: 13% ( n = 2/15); MLFS: 7% ( n = 1/15); composite complete remission (CRc): 53% ( n = 8/15); and overall response rate (ORR): 60% (9/18). Median duration of CRc and ORR: 13.15 (range: 2.4–48.7) and 14.3 months (range: 2.4–48.7), respectively, and median overall survival: 13.8 months (95% confidence interval: 3.70–23.7). Olutasidenib demonstrated encouraging response rates with a manageable safety profile for patients with post‐MPN m IDH1 AML.