Treatment with enasidenib, a small molecule inhibitor of mutant IDH2, showed promising clinical activity in patients with IDH2-mutated, high-risk myelodysplastic syndromes (MDS), according to results presented at the EHA2021 Virtual Congress. It also had a tolerable safety profile, the researchers reported.
The study included 48 patients with refractory or progressive MDS who had previously received hypomethylating agent (HMA) therapy. Participants received enasidenib 100 mg daily in 28-day cycles until disease progression, unacceptable toxicity, relapse, or transformation to acute myeloid leukemia (AML). The 22 patients with HMA-naïve higher-risk or high molecular-risk MDS, chronic myelomonocytic leukemia (CMML) or low-blast AML received enasidenib 100 mg daily plus 75 mg/m2 intravenous (IV) or subcutaneous azacitidine on days 1 through 7 of each 28-day cycle.
Nearly three-quarters of patients had high molecular-risk disease. In the combination therapy group, patients were treated for a median of four cycles (range = 2-32), compared with seven cycles (range = 1-23) in the monotherapy arm.
The most common treatment-related grade 3-4 adverse events (AEs) included neutropenia (64% in the combination group vs. 10% in the monotherapy group), thrombocytopenia (28% vs. 0%), and anemia (8% vs. 5%). Approximately 17% of patients experienced differentiation syndrome. Treatment discontinuations were most often related to disease progression (20% vs. 33%).
In the enasidenib plus azacitidine group, the overall response rate (ORR) was 84%, the complete response (CR) rate was 24%, and the partial response (PR) rate was 8%. In the enasidenib-alone arm, ORR, CR, and PR rates were 43%, 24%, and 5%, respectively. In the combination arm, after a median follow-up of 12.6 months, the median overall survival was 32.3 months, compared with 21.3 months for patients receiving enasidenib alone.
“Follow up and accrual is ongoing to better define duration and biomarkers of response,” the authors concluded.