Comparison of Patient Age Groups in Transplantation for Myelodysplastic Syndrome: The Medicare Coverage With Evidence Development Study

Abstract

Importance: In 2010, the US Centers for Medicare & Medicaid Services (CMS) indicated that data regarding efficacy of allogeneic hematopoietic stem cell transplantation (HCT) in the CMS beneficiary population with myelodysplastic syndrome (MDS) were currently insufficient, but that coverage would be provided for patients enrolled in a clinical study that met its criteria for Coverage with Evidence Development (CED).

Objective: The Center for International Bone Marrow Transplant Research (CIBMTR) submitted a study concept comparing the outcomes of patients aged 55 to 64 years vs aged 65 years or older who met those criteria, effectively providing coverage by CMS for HCT for MDS.

Design, setting, and participants: Data on patients aged 65 years or older were prospectively collected and their outcomes compared with patients aged 55 to 64 years. Patients were enrolled in the study from December 15, 2010, to May 14, 2014. The results reported herein were analyzed as of September 4, 2017, with a median follow-up of 47 months. The study was conducted by the CIBMTR. It comprises a voluntary working group of more than 420 centers worldwide that contribute detailed data on allogeneic and autologous HCT and cellular therapies.

Interventions: Patients with MDS received HCT according to institutional guidelines and preferences.

Main outcomes and measures: The primary outcome was overall survival (OS); secondary outcomes included nonrelapse mortality (NRM), relapse-free survival, and acute and chronic graft vs host disease.

Results: During the study period, 688 patients aged 65 years or older underwent HCT for MDS and were compared with 592 patients aged 55 to 64 years. Other than age, there were no differences in patient and disease characteristics between the groups. On univariate analysis, the 3-year NRM rate was 28% vs 25% for the 65 years or older group vs those aged 55 to 64 years, respectively. The 3-year OS was 37% vs 42% for the 65 years or older group vs the 55 to 64 years age group, respectively. On multivariable analysis after adjusting for excess risk of mortality in the older group, age group had no significant association with OS (HR, 1.09; 95% CI, 0.94-1.27; P = .23) or NRM (HR, 1.19; 95% CI, 0.93-1.52; P = .16).

Conclusions and relevance: Older patients with MDS undergoing HCT have similar OS compared with younger patients. Based on current data, we would recommend coverage of HCT for MDS by the CMS.

Trial registration: ClinicalTrials.gov identifier: NCT01166009.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Logan reported grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Jacoby reported personal fees from Celgene, grants and personal fees from Jazz, grants and personal fees from Sunesis, and personal fees from Novo Nordisk outside the submitted work. Dr Nishihori reported personal fees from Novartis outside the submitted work. Dr Farnia reported personal fees from Nimitt Consulting during the conduct of the study, personal fees from Nimitt Consulting outside the submitted work. Dr Weisdorf reported grants from Incyte and personal fees from Pharmacyclics outside the submitted work. Dr Horowitz reported grants from NIH, grants from Health Resources and Services Administration, personal fees from Actinium Pharmaceuticals, Adaptive Immunotherapies, Amgen, Anthem, bluebird bio, Bristol-Myers Squibb, Celgene, Chimerix, CSL Behring, CytoSen Therapeutics, Daiichi Sankyo, Gamida Cell, GlaxoSmithKline, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Kite/Gilead, Magenta Therapeutics, Mesoblast, Miltenyi, Omeros, Oncoimmune, Pfizer, Pharmacyclics, Regeneron, Sanofi Genzyme, Seattle Genetics, Shire, and Takeda Oncology during the conduct of the study; grants from Amgen outside the submitted work. Dr Rizzo reported grants from National Cancer Institute, grants from the National Heart, Lung, and Blood Institute, grants from the National Institute of Allergy and Infectious Diseases, and the Health Resources and Services Administration during the conduct of the study; grants from Office of Naval Research, Actinium Pharmaceuticals, Adaptive Biotechnologies, Amgen Inc, Anthem Inc, Astellas Pharma US, Atara Biotherapeutics, Be the Match Foundation, bluebird bio, Bristol-Myers Squibb, Boston Children's Hospital, Celgene Corp, Children's Hospital of Los Angeles, Chimerix, CSL Behring, CytoSen Therapeutics, Dana-Farber Cancer Institute, Daiichi Sankyo Co, Ltd, Fred Hutchinson Cancer Research Center, Gamida-Cell, Ltd, Gilead Sciences, Inc, GlaxoSmithKline, HistoGenetics, Inc, Immucor, Incyte Corporation, Janssen Biotech, Inc, Janssen Pharmaceuticals, Inc, Janssen Scientific Affairs, LLC, Jazz Pharmaceuticals, Inc, Karius, Inc, Karyopharm Therapeutics, Inc, Kite, a Gilead Company, Magenta Therapeutics, Medac GmbH, Mediware, Merck & Company, Inc, Mesoblast, MesoScale Diagnostics, Inc, Millennium, the Takeda Oncology Co, Miltenyi Biotec, Inc, Mundipharma EDO, National Marrow Donor Program, Novartis Oncology, Novartis Pharmaceuticals Corporation, Omeros Corporation, Oncoimmune, Inc, grants from PCORI, grants from Pfizer, Inc, grants from Phamacyclics, LLC, PIRCHE AG, Regeneron Pharmaceuticals, Inc, REGiMMUNE Corp, Sanofi Genzyme, Seattle Genetics, Shire, Sobi, Inc, Spectrum Pharmaceuticals, Inc, St. Baldrick's Foundation, Swedish Orphan Biovitrum, Inc, Takeda Oncology, University of Minnesota, University of Pittsburgh, University of Texas-MD Anderson, University of Wisconsin - Madison, and Viracor Eurofins outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Study Flowchart

HCT Indicates hematopoietic stem cell transplantation; MDS, myelodysplastic syndrome. From December 2010 to May 2014, 1929 patients with MDS aged 55 years or older received allogeneic HCT. Of those, 688 patients with Medicare were included. Patients aged 65 years or older with Medicare coverage could only get allogeneic HCT under this protocol, so all patients with Medicare were included in this analysis and no patients were excluded. The characteristics and outcomes of patients aged 65 years or older were compared with a randomly selected group of patients aged 55 to 64 years with MDS undergoing allogeneic HCT and reported to the Center for International Bone Marrow Transplant Research (CIBMTR). Patients aged 55 to 64 years were selected based on a randomization algorithm where 50% of all patients with MDS undergoing allogeneic HCT in the United States and reported to CIBMTR were included.

Figure 2.. Overall Survival by Age