Real-world treatment patterns and outcomes with olutasidenib after venetoclax in <i>IDH1</i> -mutated AML using EHR data.

Abstract

e18514 Background: Venetoclax (VEN) plus a hypomethylating agent is standard front-line therapy for patients with AML ineligible for intensive chemotherapy; however, most patients will ultimately relapse. Olutasidenib (OLU), a selective oral inhibitor of mutated IDH1 (m IDH1 ), is approved for relapsed/refractory (R/R) m IDH1 AML. In the pivotal Phase 2 trial, OLU achieved CR/CRh in 35% of patients (median CR/CRh duration 25.3 months) with acceptable tolerability. Real-world data on OLU utilization and outcomes in practice are limited. Methods: This retrospective cohort study used Loopback Analytics’ EHR database (Oct 2016 to Oct 2025), incorporating structured and unstructured data. Eligible patients were ≥18 years old with confirmed m IDH1 R/R AML, a prior VEN regimen, ≥25 days of OLU, and a documented response assessment. Treatment response was categorized as CR, CRh, CRi, or MLFS. Baseline demographics, treatment sequences, and clinical outcomes were summarized using descriptive statistics. Overall Survival (OS) and duration of response (DoR) were estimated using Kaplan-Meier methods. Results: Twenty-four OLU-treated patients met the inclusion criteria. Median age at OLU initiation was 67 years, and 63% of patients were male. Four patients (17%) received a hematopoietic stem cell transplant (HSCT) prior to OLU. Most patients (75%) presented with at least one co-occurring mutation; most commonly FLT3 (33%), NPM1 (29%), and RUNX1 (21%). Median duration of OLU treatment was 4.0 months (IQR 1.7-6.5 months) and OLU was administered as monotherapy in 54% of patients. Over half (58%) of patients received VEN as front-line therapy, primarily with HMA. OLU was second-line therapy in 42% of cases and immediately followed VEN in 83% of cases. The median number of prior lines was 2. The most common reason for OLU discontinuation was disease progression. The ORR was 58% (4 CR, 5 CRi, 1 CRh, and 4 MLFS) with a CRc rate of 42%. Among patients who achieved any response, 10 (71%) received OLU as the next line following VEN. Among patients with front-line VEN and second-line OLU, the ORR was 60% and the CRc rate was 50%. Median duration of CRc was 11.9 months (n=8 with evaluable DoR) with 2 having ongoing response at data cutoff and 2 having ongoing response at HSCT. In the overall population, four patients went to HSCT. Median OS from OLU initiation was 11.6 months, with the proportion of patients surviving 6, 9, and 12 months estimated to be 80%, 72%, and 43%, respectively. Conclusions: This study offers real-world insights into OLU treatment and outcomes in post-VEN m IDH1 R/R AML patients. OLU was used as monotherapy in half of patients, often directly following VEN. In this cohort, 58% of patients responded with 42% achieving CRc, consistent with efficacy observed in the subset of post-VEN patients from the pivotal Phase 2 trial. These findings support OLU as a viable post-VEN option, although additional data are needed.