Improved survival with enasidenib versus standard of care in relapsed/refractory acute myeloid leukemia associated with IDH2 mutations using historical data and propensity score matching analysis

Stéphane de Botton, Joseph M Brandwein, Andrew H Wei, Arnaud Pigneux, Bruno Quesnel, Xavier Thomas, Ollivier Legrand, Christian Recher, Sylvain Chantepie, Mathilde Hunault-Berger, Nicolas Boissel, Salem A Nehme, Mark G Frattini, Alessandra Tosolini, Roland Marion-Gallois, Jixian J Wang, Chris Cameron, Muhaimen Siddiqui, Brian Hutton, Gary Milkovich, Eytan M Stein, Stéphane de Botton, Joseph M Brandwein, Andrew H Wei, Arnaud Pigneux, Bruno Quesnel, Xavier Thomas, Ollivier Legrand, Christian Recher, Sylvain Chantepie, Mathilde Hunault-Berger, Nicolas Boissel, Salem A Nehme, Mark G Frattini, Alessandra Tosolini, Roland Marion-Gallois, Jixian J Wang, Chris Cameron, Muhaimen Siddiqui, Brian Hutton, Gary Milkovich, Eytan M Stein

Abstract

Background: The present study evaluated the relative survival benefits associated with enasidenib and current standard of care (SoC) therapies for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and an isocitrate dehydrogenase 2 (IDH2) mutation who are ineligible for hematopoietic stem cell transplantation (HSCT).

Methods: Propensity score matching (PSM) analysis compared survival outcomes observed with enasidenib 100 mg daily in the phase I/II AG221-C-001 trial and SoC outcomes obtained from a real-world chart review of patients in France.

Results: Before matching, enasidenib (n = 195) was associated with numerically improved overall survival (OS) relative to SoC (n = 80; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.61-1.11). After matching and adjusting for covariates (n = 78 per group), mortality risk was significantly lower with enasidenib than with SoC (HR, 0.67; 95% CI, 0.47-0.97). The median OS was 9.26 months for enasidenib (95% CI, 7.72-13.24) and 4.76 months for SoC (95% CI, 3.81-8.21). Results remained robust across all sensitivity analyses conducted.

Conclusions: PSM analyses indicate that enasidenib significantly prolongs survival relative to SoC among patients with R/R AML and an IDH2 mutation who are ineligible for HSCT. Future prospective studies are needed to validate these findings using other data sources and to assess the comparative efficacy of enasidenib for other treatment outcomes.

Trial registration: ClinicalTrials.gov NCT01915498.

Keywords: IDH2 mutations; acute myeloid leukemia; enasidenib; overall survival; standard of care.

Conflict of interest statement

SdB has received research funding and served on an advisory board for Agios; participated in speakers’ bureaus and served on advisory boards for AbbVie, Bristol Myers Squibb, and Janssen; served on an advisory board and provided consultancy to Pierre Fabre; and served on advisory boards for Astellas, Bayer, Daiichi‐Sankyo, Forma, Novartis, Pfizer, Servier, and Syros. JMB has served on advisory boards and received honoraria from Bristol Myers Squibb, Jazz Pharmaceuticals, Novartis, Otsuka, Pfizer, and Teva; and received research funding from Bristol Myers Squibb. AHW has received research funding and honoraria and served on advisory boards for AbbVie, Bristol Myers Squibb, Novartis, and Servier. AP has received honoraria from AbbVie, Amgen, Astellas, Bristol Myers Squibb, Daiichi‐Sankyo, Jazz Pharmaceuticals, Novartis, Pfizer, and Roche. BQ has received honoraria from Astellas, Celyad, Novartis, and Sunesis. CR has served on advisory boards for AbbVie, Janssen, MacroGenics, and Pfizer; served on advisory boards for and received research funding from Astellas, Bristol Myers Squibb, Daiichi‐Sankyo, Jazz Pharmaceuticals, Novartis, and Sunesis; and received research funding from Agios, Amgen, Chugai, and MaaT Pharma. MH‐B has interests in AbbVie, Astellas, Daiichi‐Sankyo, and Sunesis. NB has received honoraria from Amgen, Ariad, Jazz Pharmaceuticals, Pfizer, Shire, and Servier; and served on advisory boards for Bristol Myers Squibb. SAN, MGF, AT, RM‐G, and J(J)W are employees of Bristol Myers Squibb. CC is an employee and shareholder of EVERSANA Life Sciences Services Inc. MS is an employee of EVERSANA Life Sciences Services Inc. BH is a methodological advisor for EVERSANA Life Sciences Services Inc. GM has provided consultancy services to Bristol Myers Squibb. EMS has received consulting fees from Agios, Amgen, Astellas, Bristol Myers Squibb, Daiichi‐Sankyo, Genentech, Novartis, PTC Therapeutics, Seattle Genetics, and Syros. XT, OL, and SC have no conflicts of interest to disclose.

© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Kaplan–Meier estimate of overall survival (OS) for optimal 1:1 PS‐matched sample of patients receiving enasidenib (AG221‐C‐001 trial) and standard of care (SoC) (French chart review [FCR] study)
FIGURE 2
FIGURE 2
Comparison of overall survival (OS) as determined through various PSM algorithms

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