Journal of hematology & oncology · 2025
Olutasidenib for mutated IDH1 acute myeloid leukemia: final five-year results from the phase 2 pivotal cohort.
СтатьяКлиническое исследование II фазыМногоцентровое исследованиеПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Cortes Jorge, Curti Antonio, Fenaux Pierre, Jonas Brian A, Krauter Jürgen, Montesinos Pau, Récher Christian, Taussig David C, Wang Eunice S, Watts Justin, Wei Andrew, Yee Karen Wl, Tian Hua, Sheppard Aaron, Marzac Christophe, de Botton Stephane
Аннотация
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.
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.