Olutasidenib (OLU) for the treatment of relapsed/refractory (R/R) isocitrate dehydrogenase 1-mutant (mIDH1) acute myeloid leukemia (AML) demonstrates superior outcomes when used earlier in the treatment sequence.

These results were presented by Eunice Wang, MD, Roswell Park Comprehensive Cancer Center, Buffalo, New York, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting at Chicago, Illinois.

Previous studies have found olutasidenib efficacious for the treatment of R/R mIDH1 AML, researchers conducted a post hoc analysis of a phase 2 trial to determine the efficacy and safety of olutasidenib among patients previously treated for mIDH1 AML grouped by number of prior regimens.

The primary end points were complete remission/complete remission with partial hematologic recovery (CR/CRh), overall response rate (ORR), and overall survival (OS).

Overall, 147 patients were treated with olutasidenib 150 mg twice daily. Patients were stratified by prior lines of therapy, 93 patients had received 1 to 2 prior regimens, and 54 had received 3 or more.

Patients receiving olutasidenib after 1 or 2 regimens had a higher ORR (54%; 95% confidence interval [CI], 43.1 to 64.2 vs 39%; 95% CI, 25.9 to 53.1) and CR/CRh rate (41%; 95% CI, 30.8 to 51.5 vs 24%; 95% CI, 13.5 to 37.6) compared to those treated after ≥3 regimens. The median OS was also longer in the 1 to 2 prior regimen group than the ≥3 regimens group (13.0 months; 95% CI, 9.2 to 18.9 vs 8.9 months; 95% CI, 5.8 to 14.9).

In terms of safety, serious treatment-emergent adverse events were reported in 73% of patients who received 1 or 2 lines of prior therapy and 77.8% of patients who received ≥3 lines of prior therapy. Grade 3 or higher treatment-emergent adverse events were reported by 89.2 % of patients in the 1 or 2 regimens group and 90.7% of patients in the ≥3 regimens group. 

“Higher response rates (including CR and CRh) and greater survival were observed in patients receiving OLU following 1-2 vs ≥3 prior treatment regimens, providing rationale for initiating OLU earlier in the R/R treatment paradigm,” the researchers concluded.

Source:

Wang E, Cortes J, Wei A, et al. A phase 2 study of olutasidenib in relapsed/refractory acute myeloid leukemia: Outcomes by number of prior treatment regimens. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 6545.