Olutasidenib for mutated IDH1 acute myeloid leukemia: final five-year results from the phase 2 pivotal cohort

Autores de IIS La Fe

• Pau Montesinos Fernández

  Autor

Participantes ajenos a IIS La Fe

• Cortes, Jorge
• Curti, Antonio
• Fenaux, Pierre
• Jonas, Brian A.
• Krauter, Jurgen
• Recher, Christian
• Taussig, David C.
• Wang, Eunice S.
• Watts, Justin
• Wei, Andrew
• Yee, Karen W. L.
• Tian, Hua
• Sheppard, Aaron
• Marzac, Christophe
• de Botton, Stephane

Grupos

• Hematología y Hemoterapia

Abstract

BackgroundOlutasidenib is an oral, selective inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), FDA-approved for relapsed/refractory (R/R) acute myeloid leukemia (AML) based on a registrational, phase 2, open-label, multicenter trial. MethodsResults from the pre-planned interim analysis were previously published (data cut-off [DCO]: June 2021). In this final-follow up analysis, we report an additional 2 years of efficacy and safety data (DCO: June 2023). ResultsAt study completion, the overall population included 153 patients (median age, 71 years); 66% had received >= 2 prior treatment regimens, and 39% with a hypomethylating agent. Among the 147 efficacy-evaluable patients, 51 achieved complete remission (CR) or CR with partial hematologic recovery (CRh), resulting in a CR/CRh rate of 35% (P < 0.001; 95% CI, 27-43), with 32% of responders achieving CR. The median time to CR/CRh was 1.9 months (range, 0.9-5.6 months). Among responders, 33% achieved CR/CRh within 2-4 months and 12% required >= 4 months. The overall response rate (ORR) was 48% (n = 71; 95% CI, 40-56.7). Median duration of CR/CRh was 25.3 months (95% CI, 13.5-not reached), and median overall survival (OS) was 11.5 months (95% CI, 8.3-15.5). Patients with 1-2 prior regimens had a higher CR/CRh rate (41%) and longer median OS (13 months) than those with >= 3 prior regimens (CR/CRh: 24%; median OS: 8.9 months). CR/CRh rates were higher among patients with R132C (42%) and R132L/G/S mutations (33%) compared with those harboring R132H mutations (17%). Response rates decreased with increasing numbers of co-mutations. Few new adverse events (AEs) and no treatment discontinuations due to AEs occurred beyond Year 3. ConclusionThese 5-year data support the durable efficacy and manageable safety profile of olutasidenib in R/R mIDH1 AML, including heavily pretreated patients. Findings highlight the potential role of olutasidenib in earlier lines of treatment, and support sustaining therapy for at least 6 months to allow for a clinical response. Further research is warranted to optimize treatment sequencing and patient selection.Trial registrationNCT02719574.

© 2025. The Author(s).

Keywords

• Olutasidenib; Relapsed/refractory AML; Targeted therapy; Mutant IDH1 inhibitor