The Lynx Group

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

Conference Correspondent

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.

Related Articles


Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: