Real-world Effectiveness of Azacitidine in Treatment-Naive Patients With Higher-risk Myelodysplastic Syndromes.

Introduction: Azacitidine (AZA) is an approved frontline therapy for higher-risk myelodysplastic syndromes (HR-MDS); however, poor survival denotes unmet needs to increase depth/duration of response (DOR).
Methods: This retrospective study with patient chart review evaluated AZA effectiveness in 382 treatment-naive patients with HR-MDS from a US electronic health record (EHR)-derived database. Responses were assessed using International Working Group (IWG) 2006 criteria; real-world equivalents were derived from EHRs. Primary endpoint was IWG 2006-based complete remission rate (CRR). Secondary endpoints were EHR-based CRR, IWG 2006- and EHR-based objective response rates (ORRs), duration of CR, DOR, progression-free survival, time-to-next-treatment, and overall survival (OS).
Results: Using IWG 2006 criteria, the CRR was 7.9% (n = 30); median duration of CR was 12.0 months (95% CI, 7.7-15.6). In poor cytogenetic risk (n = 101) and TP53 mutation (n = 46) subgroups, CRRs were 7.9% (n = 8) and 8.7% (n = 4), respectively. ORR was 62.8% (n = 240), including a hematologic improvement rate (HIR) of 46.9% (n = 179). Using EHR-based data, CRR was 3.7% (n = 14); median duration of CR was 13.5 months (95% CI, 4.5-21.5). ORR was 67.8% (n = 259), including an HIR of 29.3% (n = 112). Median follow-up was 12.9 months; median OS was 17.9 months (95% CI, 15.5-21.7).
Conclusions: Consistent with other studies, CRRs and median OS with AZA in treatment-naive patients with HR-MDS were low in this large, real-world cohort. Novel agents/combinations are urgently needed to improve these outcomes in HR-MDS.
Competing Interests: Disclosure N.R., S.M., S.I., M.C., and R.K. are current equity holders at Gilead Sciences Inc. and were employed by Gilead Sciences Inc. at the time of this study. A.H.W. receives institutional research funding from Abbvie, Amgen, Astex, Astra Zeneca, BMS, Novartis, Servier, and Syndax; is an employee of the Walter and Eliza Hall Institute, and is eligible for a fraction of the royalty stream related to venetoclax; serves on speaker's bureaus for Abbvie, Astellas, BMS, and Novartis; and served on advisory boards for Abbvie, Agios, Amgen, Astellas, BMS, Gilead Sciences Inc., Janssen, Macrogenics, Novartis, Pfizer, Roche, and Servier. D.A.S. received consulting fees from AbbVie, Affimed, Gilead Sciences Inc., Incyte, Intellisphere, Molecular Partners, PGEN Therapeutics, Takeda, and Zentalis; served on advisory boards for AvenCell, Bluebird Bio, BMS, Intellia, Jasper Therapeutics, Kite, Magenta Therapeutics, Nkarta, Novartis, Shattuck Labs, Servier, Syndax, and Syros; and has financial or nonfinancial interests in Aprea, Jazz, and Moffit. M.G. served on advisory boards for GSK, Janssen, Karyopharm, Sanofi, and TG Therapeutics. N.G.D. receives institutional research funding from AbbVie, Amgen, Astellas, Bristol-Meyers Squibb, Daiichi-Sankyo, FATE Therapeutics, Genentech, Gilead Sciences Inc., Glycomimetics, Hanmi, ImmunoGen, Novimmune, Pfizer, Servier, Trillium, and Trovagene; and received consulting fees from AbbVie, Agios, Amgen, Arog, Astellas, Bristol-Meyers Squibb, Celgene, Daichii-Sankyo, Genentech, Gilead Sciences Inc., ImmunoGen, Jazz, Novartis, Pfizer, Servier, Shattuck Labs, Syndax, and Trillium. Y.W. has received support for the current study from Gilead Sciences Inc.; and is a current equity holder in McKesson. P.V. has received support for the current study from Gilead Sciences Inc. and Scimentum.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)