Hypomethylating agent (HMA) therapy use and survival in older adults with Refractory Anemia with Excess Blasts (RAEB) in the United States (USA): a large propensity score-matched population-based study^†

Abstract

Hypomethylating agents (HMA) showed overall survival (OS) benefits in patients with higher-risk myelodysplastic syndromes (HR-MDS) in clinical trials. We conducted a retrospective cohort study of Surveillance, Epidemiology, and End Results (SEER)-Medicare data of patients ≥66 years diagnosed with refractory anemia with excess blasts (RAEB), a proxy for HR-MDS, in 01/2001–04/2004 (pre-period) or 01/2006–12/2011 (post-period). Association between post-period diagnosis and OS was examined using propensity scores (PS)-matched samples. Among 1876 RAEB patients, median OS was 9 months and 30.8% received HMAs (3.6% in pre-period; 43.0% in post-period) with no association between post-period diagnosis and OS. In the top PS quartile, post-period diagnosis was associated with a 74% lower risk of death (Hazard ratio [HR] = 0.26, 95%-CI: 0.10–0.69, p = 0.007), while outcomes were worse in the lowest PS quartile (HR = 2.80, 95%-CI: 1.06–7.36, p = 0.037). HMA lead to a 3-month OS benefit for patients most likely to receive HMA but not for unselected RAEB cohort.

Keywords:

• Myelodysplastic syndromes
• survival
• effectiveness
• hypomethylating agents (HMA)
• azacitidine
• SEER-Medicare

Data sharing

SEER-Medicare data cannot be shared by the authors as directed by the SEER-Medicare data use agreement. Data may be requested directly from the National Cancer Institute. However, we are open to sharing our methodology and analytical approaches upon request.

Disclosure statement

AJD reports grants from Celgene during the conduct of the study; and a family member with personal fees from Abbvie, Jazz Pharmaceuticals, Kyowa Hakko Kirin, Tolero Pharmaceuticals, and Daiichi Sankyo to family members outside of the submitted work. RW received research funding from Celgene Corp. NAP received research funding (institutional) from Boehringer Ingelheim, Astellas Pharma, Daiichi Sankyo, Sunesis Pharmaceuticals, Celator, Pfizer, Astex Pharmaceuticals, CTI BioPharma, Genentech, AI Therapeutics, Samus Therapeutics, Arog Pharmaceuticals and Kartos Therapeutics. NAP received research funding from Celgene. NAP had a consultancy with and received honoraria from Alexion, Pfizer, Agios Pharmaceuticals, Blueprint Medicines, Incyte, Novartis and Celgene. SFH received research funding (institutional) from Celgene, TG Therapuetics, DTRM, Genentech. SFH reports personal fees from Celgene, personal fees from Pharmacyclics, personal fees from Genentech, personal fees from Bayer, outside the submitted work; SDG has consulted for and receives research funding from Celgene; personal fees from Abbvie, Jazz Pharmaceuticals, Kyowa Hakko Kirin, Tolero Pharmaceuticals, and Daiichi Sankyo outside of submitted work. XM received research funding from Celgene Corp, which supported the development of this manuscript, and consulted for Celgene and Incyte. AMZ received research funding (institutional) from Celgene, Acceleron, Abbvie, Otsuka, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene, Incyte, Takeda, ADC Therapeutics. AMZ had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene, Ariad, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Trovagene, BeyondSpring, and Takeda. The other authors have no conflicts of interest to declare.

Author contributions

AMZ designed the research, supervised data analysis, interpreted the data and wrote the manuscript. AJD designed the research, supervised data analysis, interpreted the data, and wrote the manuscript. XH helped to design the study, analyzed and interpreted the data, and critically reviewed the manuscript. All other authors reviewed the data and critically reviewed and contributed to the manuscript significantly. All authors approved the final manuscript for submission.

Additional information

Funding

AMZ is a Leukemia and Lymphoma Society Scholar in Clinical Research and is also supported by a NCI’s Cancer Clinical Investigator Team Leadership Award (CCITLA). This research was partly funded by the Dennis Cooper Hematology Young Investigator Award (AZ), and was in part supported by the National Cancer Institute of the National Institutes of Health under Award Number P30 CA016359. The collection of the California cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute (NCI)'s Surveillance, Epidemiology and End Results (SEER) Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. The authors acknowledge the efforts of the Applied Research Program, National Cancer Institute; the Office of Research, Development and Information, Centers for Medicare and Medicaid Services; Information Management Services, Inc.; and the SEER Program tumor registries in the creation of the SEER-Medicare database. The interpretation and reporting of the SEER-Medicare data are the sole responsibility of the authors.