The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Hematology Advisor‘s conference coverage.

Among patients with high-risk, isocitrate dehydrogenase 2 (IDH2)-mutated myelodysplastic syndromes (MDS), enasidenib, particularly in combination with azacitidine, may improve clinical outcomes, according to research presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Five percent of patients with MDS harbor an IDH2 mutation. Enasidenib, a selective inhibitor of mutant IDH2, has previously shown activity among patients with relapsed or refractory acute myeloid leukemia. For this open-label phase 2 study ( Identifier: NCT03383575), researchers evaluated the safety and efficacy of both single-agent enasidenib and an enasidenib-azacitidine combination among patients with IDH2-mutant MDS.

Overall, 48 patients have been enrolled and stratified by disease characteristics to receive enasidenib and azacitidine (26 patients) or enasidenib alone (22 patients). Patients in the combination group were naïve to hypomethylating agent treatment and patients in the single-agent group had treatment failure to hypomethylating agents.

Continue Reading

The median patient age was 73 years (range, 46-83), and 72% of patients were classified as high molecular risk because of an ASXL1 (39%) or RUNX1 (17%) mutation. In the combination and single-agent arms, the median numbers of treatment cycles were 4 and 7, respectively.

The median follow-up was 12.6 months, after which 46 patients were evaluable for a response. In the enasidenib/azacitidine and enasidenib only arms, the overall response rates were 84% and 43%, respectively, though 24% of patients in each group had a complete remission. Zero patients in the combination group vs 10% of patients in the single-agent group had progressive disease.

The median OS in the enasidenib and azacitidine group was 32.2 months vs 21.3 months in the enasidenib only group.

Grade 3-4 adverse events were, however, more common in the combination group, including neutropenia (64% vs 10% in the single-agent group), thrombocytopenia (28% vs 0%, respectively), anemia (8% vs 5%, respectively), and infection (32% vs 14%, respectively).

IDH differentiation syndrome was noted in 12% of patients in the combination group vs 24% of patients in the single-agent group.

Enrollment in the trial is ongoing, according to the authors.

Disclosure: Some [or one] study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Read more of Hematology Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.


Venugopal S, Dinardo CD, Takahashi K, et al. Phase II study of the IDH2-inhibitor enasidenib in patients with high-risk IDH2-mutated myelodysplastic syndromes (MDS). J Clin Oncol. 2021;39:(suppl 15; abstr 7010). doi:10.1200/JCO.2021.39.15_suppl.7010