Treatment patterns and outcomes with olutasidenib after venetoclax in IDH1-mutated AML using real-world data from a chart review.

e18527 Background: Olutasidenib (OLU), a selective oral inhibitor of mutant IDH1 (m IDH1 ), is a key treatment option for patients with m IDH1 mutated acute myeloid leukemia (AML). Targeted agents are used for patients following failure of chemotherapy or front-line venetoclax (VEN)-based regimens. OLU is approved for relapsed/refractory (R/R) m IDH1 AML. In the pivotal Phase 2 trial (NCT02719574), OLU achieved CR/CRh in 35% of patients, with a median duration of CR/CRh of 25.3 months and acceptable tolerability; however, real-world data on OLU utilization and outcomes post-VEN remain limited. Methods: This retrospective cohort study used data from a physician-based chart review. Eligible patients were ≥18 years old and had R/R AML with an IDH1 mutation, prior treatment with VEN, initiated OLU between December 2022 – March 2025, and were assessed for a response. Patients were excluded if they received prior IDH1 targeted therapy or >1 additional therapy between receipt of VEN and OLU. Patient disease characteristics, prior treatment history, and effectiveness and safety outcomes were summarized using descriptive statistics. Duration of response was estimated using Kaplan-Meier (KM) methods. Results: Fifty-one charts were collected from 18 physicians. The median patient age at diagnosis was 61 years and 78% were male. The median follow-up time from diagnosis was 23.6 months. ECOG was 0-1 in 54.9% and 2-3 in 45.1% of patients at time of OLU initiation and 15.7% had AML with antecedent MDS. Most patients (60.8%) harbored at least one co-mutation, the most common being DNMT3A (43.1%), FLT3 (35.3%) and NPM1 (35.3%). Most patients (90.2%) received VEN-based therapy in the first-line; overall, ORR was 81.3% and a CR/CRi of 47.9%. The median duration of prior VEN treatment was 4.2 months (IQR, 1.6-16.2 months). OLU was mostly given as monotherapy (96.1%) and in the second line (72.5%), with 27.5% given as third-line treatment. Median OLU treatment duration was 12.6 months (IQR, 7.2-20.1 months). The ORR for OLU was 90.2%, with 60.8% CR/CRh and 57% CR, with a median CR/CRh DOR of 30.3 months. Of the 36 (70.6%) patients who were RBC and/or platelet transfusion dependent at baseline, 20 (55.6%) achieved transfusions independence while on OLU. Of the 12 patients discontinuing OLU, the primary reason was disease progression (41.7%). The most common adverse events were fatigue (11.8%), infection, neutropenia, and nausea (each 7.8%). Conclusions: OLU demonstrated robust real-world effectiveness in adults with R/R m IDH1 AML previously treated with VEN, a subgroup that historically has very poor outcomes, with a CR/CRh rate of 60.8% and a median response duration of 30.3 months. Substantial reductions in transfusion dependence further support OLU as a viable post-VEN therapeutic option. These findings suggest that earlier sequencing of OLU in the treatment paradigm may optimize patient outcomes.