The combination of olutasidenib plus azacitidine produced “durable” responses in patients with relapsed or refractory mIDH1 acute myeloid leukemia (AML), according to a pooled analysis of a phase 1/2 trial.
“Olutasidenib in combination with azacitidine induced high response rates and durable remissions with a well-characterized and manageable side effect profile in patients with R/R IDH1-mutated AML,” the investigators, led by Jorge Cortes, MD, director of the Georgia Cancer Center in Augusta, wrote in the article that was recently published in the Journal of Hematology and Oncology.
The US Food and Drug Administration approved olutasidenib, a potent, selective, oral, small-molecule inhibitor of mIDH1, in 2022. The approval was based on the pivotal phase 2 trial assessing olutasidenib monotherapy in patients with relapsed or refractory AML.
In this analysis, Dr. Cortes and colleagues report the results of the phase 1 and phase 2 studies of patients with relapsed or refractory mIDH1 AML who received the combination regimen of olutasidenib and azacitidine.
Pooled analysis
In the pooled analysis, 67 adult patients with mIDH1 AML received 150 mg olutasidenib twice daily plus the hypomethylating agent (HMA) azacitidine. The median age of the patients was 66 years old and 54% were male. Of the patients, 83% had at least two prior regimens, including an HMA, IDH1 inhibitor therapy, and hematopoietic stem cell transplant.
The combination therapy induced overall responses in 51% of patients and a durable complete remission (CR) or complete remission with partial hematologic recovery (CRh) in 31% of the patients, according to the investigators, who noted that “transfusion independence was achieved in all response groups, including patients with non-CR/CRh responses or no response.”
Analysis limitations
Dr. Cortes and colleagues wrote that some of the limitations of the analysis included a small sample size and the possibility that the heterogeneous patient population present in the trial might confound the therapy response. In addition, some patients stopped combination therapy early because they went into remission and moved on to a stem cell transplant (HSCT), which may have truncated the duration of response, according to the investigators.
“The observed efficacy is clinically meaningful and represents a new molecularly targeted therapeutic option for a patient population that has a poor prognosis and limited treatment options,” Dr. Cortes and colleagues concluded.
Reference
Cortes JE, Roboz GJ, Baer MR, et al. Olutasidenib in combination with azacitidine induces durable complete remissions in patients with relapsed or refractory mIDH1 acute myeloid leukemia: a multicohort open-label phase 1/2 trial. J Hematol Oncol. 2025;18(1):7. 2025. doi:10.1186/s13045-024-01657-z
