Effectiveness of olutasidenib versus ivosidenib in patients with mutated isocitrate dehydrogenase 1 acute myeloid leukemia who are relapsed or refractory to venetoclax: the 2102-HEM-101 trial versus a US electronic health record-based external control arm.

First-line venetoclax (VEN) treatment for acute myeloid leukemia (AML) has high relapse rates, with limited evidence guiding subsequent therapy sequencing. This study evaluated the effectiveness of olutasidenib (OLU) versus ivosidenib (IVO) for patients withIDH1 relapsed/refractory (R/R) AML previously treated with VEN based therapy. Outcomes were compared between a subcohort of OLU-treated patients from the 2102-HEM-101 trial and an external control arm of IVO-treated patients from the Loopback Analytics electronic health record database. Entropy balancing was applied to align key prognostic variables. Risk differences (RD) for response/TI were estimated via logistic regression, and hazard ratios (HR) for OS via Cox regression. Following weighting, treatment with OLU versus IVO was associated with significantly higher rates of complete response (RD: 0.25; 95%CI: 0.01, 0.49), transfusion independence (RD: 0.27; 95%CI: 0.01, 0.53), and OS (HR: 0.33; 95%CI: 0.11, 0.94). Results suggest favorable effectiveness of OLU versus IVO in this population.