AML-437 Real-World Effectiveness of Enasidenib (ENA) in Older Patients With Relapsed/Refractory (R/R) Isocitrate Dehydrogenase-2 (IDH2)-Mutated Acute Myeloid Leukemia (AML)

Abstract

Older age at first relapse and Black race are prognostic indicators of worse survival for patients with AML. ENA was the first drug approved in the United States (US) for the treatment of adults with R/R IDH2-mutated AML. This study assessed real-world clinical outcomes in patients with onset of R/R IDH2-mutated AML at ≥60 years of age who received ENA versus other therapies as first-line (1L) R/R AML treatment. Black patients were assessed as a subgroup. This physician-abstracted, retrospective, multisite, chart-review study was conducted in US-based community oncology practices. Patients receiving 1L ENA between 01/2018 and 06/2019, or other 1L therapy between 01/2016 and 07/2017, were selected for analysis. Physician-reported 1L-therapy response and dates corresponding to 1L-therapy start, progression, and death were collected from patient charts. Overall response rate (ORR; complete or partial response, morphological leukemia-free state) was calculated; adjusted odds of achieving response was estimated by multivariate logistic regression. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method; adjusted risk of progression and death were estimated by multivariable Cox proportional hazard models. Treatment-group differences in PFS and OS in the Black patient subgroup were assessed using the log-rank test. Of 128 eligible patients, 87 received ENA and 41 received other 1L R/R therapy. Compared with other 1L therapies, ENA was associated with higher ORR (74% versus 34%, P<0.01; adjusted odds ratio, 11.72 [95% CI, 2.8-49.1], P<0.01), longer median PFS (8 versus 3 months, after a median follow-up of 9 and 7 months, respectively; adjusted HR, 0.31 [95% CI, 0.19-0.53], P<0.01), and longer median OS (9 versus 6 months; adjusted HR, 0.31 [95% CI, 0.18-0.53], P<0.01). Similar trends were observed in the Black patient subgroup (ENA, n=19; other 1L therapy, n=8) for median PFS (8 versus 3 months, respectively; P<0.01) and median OS (10 versus 4 months; P<0.01). This is the first real-world study to demonstrate superior OS, PFS, and ORR benefits for older patients with R/R IDH2-mutated AML treated with ENA versus other 1L therapies. PFS and OS benefits of ENA treatment remained consistent in the Black patient subgroup.