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

6528 Background: Olutasidenib is a potent, selective, oral inhibitor of mIDH1 and is FDA-approved for relapsed/refractory (R/R) acute myeloid leukemia (AML) based on a registrational, Phase 2, open-label, multicenter trial (NCT02719574). We report final five-year results from the pivotal cohort. Methods: In the pivotal cohort of the Phase 2 trial, patients with mIDH1 AML received olutasidenib 150mg BID. Primary endpoint was complete remission (CR) + CR with partial hematologic recovery (CRh) by modified IWG Criteria 2003. Data cutoff: May 15, 2023. Results: Baseline characteristics of 153 enrolled patients are shown in Table. Of 147 efficacy evaluable patients, CR was achieved in 32% (95% CI: 24.5, 40.2) and CR/CRh in 35% (95% CI: 27, 43; P<0.0001). Median time to CR/CRh was 1.9 mo (range: 0.9, 5.6). The median duration of CR/CRh was 25.3 mo (95% CI: 13.5, not reached), with maximum duration 54.6 mo. Overall response rate was 48% (95% CI: 40, 56.7), with median duration 15.5 mo (95% CI: 7.4, 26.2) and maximum duration 54.6 mo. Median overall survival was 11.6 mo (95%CI: 8.9, 15.5). In the 12 patients R/R to prior venetoclax, 33% achieved a CR/CRh; median duration of CR/CRh is not reached (ongoing at 54.3 months), and median overall survival is 16.2 months (95%CI: 2.6, not reached). Transfusion independence from red blood cells and platelets was achieved in 34 of 87 (39%) patients and 28 of 69 (41%) patients, respectively, who were dependent at baseline. 16 (11%) patients proceeded to stem cell transplant. The 5-year safety profile was consistent with what was previously reported. The most common AEs (% reported over 3 years and over the full 5 years) were: febrile neutropenia (22% and 22%), constipation (26% and 27%), diarrhea (20% and 21%), nausea (38% and 39%), fatigue (23% and 23%), pyrexia (24% and 24%), hypokalaemia (20% and 22%), red blood cell count decreased (26% and 26%), white blood cell count increased (25% and 25%). Differentiation syndrome was reported in 14% by Year 3, with no new events by Year 5. The safety profile was stable with long-term follow up. Conclusions: This analysis provides an additional 2 years of data beyond the results that led to FDA approval of olutasidenib. This first report of the five-year data further demonstrates the rapid and durable responses observed with olutasidenib in heavily pretreated patients with mIDH1 AML, including those R/R to prior venetoclax. Clinical trial information: NCT02719574 . Table: see text