PS1026 ENASIDENIB ASSOCIATED WITH IMPROVED SURVIVAL COMPARED WITH STANDARD OF CARE FOR R/R AML PATIENTS WITH AN IDH2 MUTATION BASED ON DATA FROM STUDY AG221‐C‐001 AND A REVIEW OF PATIENT CHARTS IN FRANCE
Authors: S. de Botton, J. Brandwein, A. Wei, S. Abi Nehme, M. Frattini, A. Tosolini, R. Marion‐Gallois, J.J. Wang, C. Cameron, M. Siddiqui, B. Hutton, G. Milkovich, E. Stein
Journal: HemaSphere (2019)

Background: Enasidenib is approved for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with an isocitrate dehydrogenase‐2 (IDH2) mutation. Supporting data for the use of enasidenib in patients with R/R AML and an IDH2 mutation are available from the phase 1/2 AG221‐C‐001 single‐arm study (NCT0915498); direct comparative efficacy data for enasidenib are not available. Aims: To compare the overall survival (OS) associated with enasidenib 100 mg daily and standard of care (SoC) in patients with R/R AML and an IDH2 mutation not eligible for hematopoietic stem cell transplantation (HSCT). Methods: Propensity score matching (PSM) analysis was conducted using individual patient data (IPD) for patients treated with 100 mg of enasidenib daily from the phase 1/2 AG221‐C‐001 study, and IPD for real‐world patients treated with SoC from a review of patient charts at 9 French sites. Covariates selected for calculating propensity scores (PS) included history of HSCT before baseline, age, number of prior lines of AML therapy at baseline, cytogenetic risk at baseline, and history of myelodysplastic syndromes. For the primary analysis, PSM was performed using optimal 1:1 matching and excluded patients undergoing HSCT after baseline. Hazard ratios (HRs) were estimated from Cox proportional hazards models that adjusted for PS covariates in matched populations. Robustness of results was assessed by a range of sensitivity analyses including different matching algorithms and other prognostic factors. Results: Prior to performing PSM, considerable differences between patients treated with enasidenib (N = 195) and patients treated with SoC (N = 80) were observed with respect to number of prior lines of therapy, prior HSCT, and cytogenetic risk profile, as determined by higher standard mean differences (SMDs) in the pre‐matched population compared with the post‐matched population. Before PSM, patients treated with enasidenib had improved OS compared with SoC (HR 0.82; 95% confidence internal [CI] 0.61–1.11). After matching (enasidenib n = 78; SoC n = 78) and adjusting for covariates, mortality risk was significantly lower for enasidenib compared with SoC and the 95% CI excluded the value 1 (HR 0.67, 95% CI 0.47–0.97). The median survival time for enasidenib was 9.3 months (95% CI 7.7–13.2) compared with 4.8 months (95% CI 3.8–8.2) for SoC (Figure). All sensitivity analyses had mortality HR point estimates that were in favor of enasidenib and excluded 1 from their respective 95% CI in most cases. The results from the sensitivity analyses were consistent with the primary analysis. Summary/Conclusion: Patients with R/R IDH2‐mutated AML not eligible for HSCT who were treated with enasidenib on study had improved survival compared with patients receiving SoC in a real‐world setting. Future studies are needed to validate these findings using other data sources, to compare enasidenib with specific treatments and to assess the comparative efficacy of enasidenib for other outcomes. image