Continuing Enasidenib Treatment Improves Survival and Responses for Mutant-IDH2 R/R AML Patients with Stable Disease

Conference Correspondent - ASH 2017


Enasidenib (AG-221) is a novel, small-molecule oral inhibitor of mutant IDH2 (mIDH2) proteins that is currently indicated for the treatment of adult patients with mIDH-positive relapsed or refractory (R/R) acute myeloid leukemia (AML). This analysis reports the response and survival outcomes of enasidenib 100 mg daily in a subset of patients who maintained stable disease (SD) in the first 90 days of treatment of the phase 1/2 AG221-C-001 study.

In this study, SD was defined by the European LeukemiaNet 2017 criteria (ie, showing no formal International Working Group response and no evidence of progressive disease [PD] for at least 90 days). Eligible patients were classified into 3 patient subgroups: SD Late Responders, who attained a hematologic response at any later time; SD Only, who continued to maintain persistent SD after day 90; and PD After Day 90, who progressed after day 90.

Among the 214 enasidenib-treated patients with mIDH2 R/R AML, 89 (42%) patients maintained SD for the first 90 days of treatment. Of these, the SD Late Responders cohort included 24 (27%) patients, the SD Only cohort included 40 (45%) patients, and the PD After Day 90 cohort included 25 (28%) patients.

In the SD Late Responders cohort (n = 24), 14 patients achieved complete remission (CR), 3 had CR with incomplete platelet recovery, 3 had first-ever morphologic leukemia-free state, and 4 had partial responses. Median treatment duration was 250.5 days (range, 112-717 days); median time to first response was 129.5 days (range, 90-336 days). Median treatment duration in the SD Only group was 173 days (range, 99-361 days), and 107 days (range, 66-218 days) in the PD After Day 90 group.

In terms of survival outcomes, the median overall survival (OS) was 9.0 months for the entire SD patient cohort (n = 89). In the SD Late Responders cohort, the median OS was 26.7 months (95% confidence interval [CI], 10.7-26.7), and the estimated 1-year survival rate was 61.3% (95% CI, 37.9-84.7). In the SD Only group, median OS was 8.8 months (95% CI, 7.7-11.6), and the estimated 1-year survival was 26.0% (95% CI, 8.1-43.9). The median OS was 5.8 months (95% CI, 5.4-8.3), and the estimated 1-year survival was 0% in the PD After Day 90 group.

Patients in the SD Late Responders group showed a significant OS benefit compared with those in the PD After Day 90 group, with an 84% decreased risk for death (hazard ratio [HR], 0.16; 95% CI, 0.07-0.39); compared with the SD Only group, the SD Late Responders group had a 61% decreased risk for death (HR, 0.39; 95% CI, 0.18-0.85). Compared with the PD After Day 90 group, patients in the SD Only group showed a 57% reduction in the risk for death (HR, 0.43; 95% CI, 0.23-0.80).

The authors concluded that SD during early treatment with enasidenib does not predict treatment failure, and patients who maintain SD may derive benefit from continuing enasidenib treatment for at least 6 cycles or until disease progression.

Stein EM, et al. 2017 ASH. Abstract 1299.