The FDA granted priority review of enasidenib for patients with relapsed/refractory IDH2-mutated acute myeloid leukemia (AML).
The decision was based on results of the single-arm, phase I/II AG221-C-001 study, which included 198 patients (median age = 69 years) with relapsed/refractory AML (70%), untreated AML (17%), myelodysplastic syndromes (7%), or another IDH2-mutant hematologic malignancy (6%).
Patients received a median of two prior therapies (range = 1-6 therapies), and 64 percent received ≥2 prior therapies. Enasidenib was administered at escalating doses, increasing from 30 mg or 50 mg once or twice daily to the highest dose of 450 mg daily. Though a maximum tolerated dose was not reached, the dose selected for future studies was 100 mg once daily.
Among 181 evaluable patients (including 128 with relapsed/refractory AML), the objective response rate was 41 percent in enasidenib-treated patients. The complete response (CR) rate was 18 percent, with 1.6 percent of patients achieving a CR with incomplete platelet recovery or incomplete blood count recovery. Fourteen percent of patients had a partial response (PR).
The median duration of response was 6.9 months; in those with relapsed/refractory AML, the median duration was six months (95% CI 3.7-9.2).
Overall, eight patients went on to receive HCT, five of whom had relapsed/refractory AML. The most common treatment-related AEs were indirect hyperbilirubinemia (19%) and nausea (18%).
Source: Celgene press release, March 1, 2017.