Olutasidenib ± azacitidine as a bridge to allo-HSCT in R/R IDH1-mutated AML: A phase I/II study

Results from a post hoc analysis of an open-label, multicenter, phase I/II study (NCT02719574) evaluating olutasidenib (Olu) alone or in combination with azacitidine (Olu + Aza) as a bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 223 adults with relapsed/refractory (R/R) IDH1-mutated (IDH1m) acute myeloid leukemia (AML) were published in the European Journal of Haematology by Dinner et al. The primary endpoint was complete remission (CR) or CR with partial hematologic recovery (CRh) rate.

Key data: Among all patients, 13% proceeded to allo-HSCT (Olu, n = 19; Olu + Aza, n = 11). Prior to allo-HSCT, 73% achieved CR/CRh, and the overall response rate (ORR) was 97% (95% confidence interval [CI], 82.8–99.9). CR/CRh and ORR were similar between treatment groups. With a median follow-up of 36 months, median OS from treatment initiation was not reached (NR; 95% CI, 17.4–NR), with estimated OS rates of 90% and 58% at 12 and 24 months, respectively. With a median post-allo-HSCT follow-up of 29.1 months, median OS post-allo-HSCT was NR (95% CI, 15.1–NR). Estimated OS at 6 and 12 months post-allo-HSCT was 94% and 87%, respectively, in the Olu group, and 81% at both timepoints in the Olu + Aza group. Treatment was generally well tolerated, with safety profiles consistent with those previously reported for Olu and Olu + Aza.

Key learning: Olu and Olu + Aza had manageable safety profiles in patients with R/R IDH1m AML and demonstrated efficacy as a bridge to allo-HSCT, with encouraging CR/CRh rates achieved prior to transplant.