Patients with relapsed/refractory mIDH1 AML who proceeded to transplant after olutasidenib treatment.

e18516 Background: Hematopoietic stem cell transplantation (HSCT) in post-remission AML is potentially curative and can improve survival for patients at high risk of relapse. However, achieving remission in patients with relapsed/refractory (R/R) AML is difficult, and therapies that enable previously ineligible patients to proceed to HSCT are highly desired. Olutasidenib (OLU) is FDA-approved for treatment of R/R mIDH1 AML. In the pivotal cohort of the registrational, Ph2, open-label, multicenter trial of olutasidenib, 35% of patients achieved complete remission (CR) or CR with partial hematologic recovery (CRh) with a 25.9 mos duration of response. Here we report the characteristics and outcomes of patients treated with olutasidenib who then underwent HSCT. Methods: In the Phase 2 trial, the pivotal cohort enrolled adults with R/R m IDH1 AML. OLU was administered at 150 mg BID in continuous 28-day cycles. The primary efficacy endpoint was the CR/CRh rate. Patients who achieved remission and met criteria for transplant could proceed to HSCT with discontinuation of OLU. Data cutoff: June 18, 2021. Results: 153 patients with m IDH1 R/R AML received OLU monotherapy, and 16 (11%) proceeded to HSCT. In these 16 patients, median age was 61 (40, 67), 50% were male, and median BMI was 24 (18, 38). Baseline bone marrow blast count was 24% (6% - 60%). At baseline, 15/16 (94%) had intermediate cytogenetic risk and 1 was unknown. Time since diagnosis was 8.2 mos (1.5, 116.8). 8 (50%) were refractory and 8 were relapsed (2 for >12 months). Median number of prior regimens was 2 (range 1-7). All 16 had prior induction, 2 (13%) had prior HMA, 3 (19%) had prior HSCT, and 94% (15/16) had prior intensive chemotherapy (IC), 50% (n=8) of whom were IC-refractory. Response rates to OLU in the 16 patients prior to proceeding to HSCT were 75% CR/CRh (69% CR), 19% patients CRi and 6% stable disease (see Table). All 16 patients were alive at 100 days. Median survival from start of OLU treatment has not been reached. Overall survival probability was 94% (95%CI: 63, 99) at 12 months and 61% (95% CI: 32, 80) at 24 months. The safety profile of this subpopulation was consistent with the rest of the cohort. No deaths due to an adverse event occurred. Conclusions: Olutasidenib was effective in achieving remission in patients with mIDH1 R/R AML, thus enabling patients R/R to or ineligible for intensive chemotherapy at study entry to proceed to potentially curative HSCT. Clinical trial information: NCT02719574 . Table: see text