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

Cortes, J; Curti, A; Fenaux, P; Jonas, BA; Krauter, J; Montesinos, P; R&#233;cher, C; Taussig, DC; Wang, ES; Watts, J; Wei, A; Yee, KW; Tian, H; Sheppard, A; Marzac, C; De Botton, S

Author(s): Cortes, J; Curti, A; Fenaux, P; Jonas, BA; Krauter, J; Montesinos, P; Récher, C; Taussig, DC; Wang, ES; Watts, J; Wei, A; Yee, KW; Tian, H; Sheppard, A; Marzac, C; De Botton, S;
Details: Publication Year 2025-11-14,Volume 18,Issue #1,Page 102
Journal Title: Journal of Hematology & Oncology
Abstract: BACKGROUND: Olutasidenib 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. METHODS: Results 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). RESULTS: At 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. CONCLUSION: These 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 REGISTRATION: NCT02719574.
Keywords: Humans; *Leukemia, Myeloid, Acute/drug therapy/genetics; *Isocitrate Dehydrogenase/genetics/antagonists & inhibitors; Aged; Male; Female; Middle Aged; Aged, 80 and over; *Mutation; Adult; *Pyridines/therapeutic use/adverse effects; *Antineoplastic Agents/therapeutic use; Follow-Up Studies; Mutant IDH1 inhibitor; Olutasidenib; Relapsed/refractory AML; Targeted therapy
Research Division(s): Blood Cells and Blood Cancer
PubMed ID: 41239466
Publisher's Version: https://doi.org/10.1186/s13045-025-01751-w
Open Access at Publisher's Site: https://doi.org/10.1186/s13045-025-01751-w
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-12-02 09:39:26

Last Modified: 2025-12-02 09:40:42