A natural history of lower-risk myelodysplastic syndromes with ring sideroblasts: an analysis of the MDS-CAN registry

Abstract

Patients with lower-risk (LR) myelodysplastic syndromes (MDS) with ring sideroblasts (RS) have better prognosis than those without RS, but how they fare over time is not fully understood. This study’s objective was to assess the natural history of LR MDS with RS ≥5% using MDS-CAN registry individual data. Kaplan–Meier estimates and generalized linear mixed models were used to describe time-to-event outcomes and continuous outcomes, respectively. One hundred and thirty-eight patients were enrolled; median times from diagnosis to enrollment and follow-up were 6.6 and 39.6 months, respectively. Within 5 years of enrollment, 65% of patients had ≥1 red blood cell transfusion dependence episode. Within 5 years of diagnosis, 59% developed iron overload, 38% received iron chelation therapy, 14% progressed to acute myeloid leukemia, and 42% died. Patients exhibited inferior health-related quality of life trends. These first real-world data in LR MDS-RS in Canada indicate a high level of morbidity and mortality over a 5-year period. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02537990

Keywords:

• Lower-risk myelodysplastic syndromes
• ring sideroblasts
• natural history
• overall survival
• Canadian MDS registry

Acknowledgments

The authors received editorial support in the preparation of this manuscript from Saba Choudhary, PhD, of Excerpta Medica, funded by Bristol Myers Squibb. The authors would like to thank all the patients and their families, nurses, study personnel, and investigators who participated in the MDS-CAN Registry and made this study possible, the clinical study teams who participated in the study, and the protocol managers for this study. The authors would also like to thank Celgene Inc., a Bristol-Myers Squibb Company, Canada for unrestricted funds that help support the registry operational costs.

Author contributions

R.B., C.W., C.C., P.S., and D.T. conceived the study, were involved in the conduct of the study; R.B., L.C., L.M., K.W.L.Y., M.G., N.Z., A.S., H.A.L., G.C., V.B., L.B., D.K., E.S-H., N.F., T.N., M-M.K., J.S., R.D., A.P., A.T., M.S., and A.M. performed data acquisition; P.S. analyzed the data; R.B., L.C., L.M., K.W.L.Y., M.G., N.Z., A.S., H.A.L., G.C., V.B., L.B., D.K., E.S-H., N.F., T.N., M-M.K., J.S., R.D., C.W., C.C., P.S., and D.T. interpreted the data. All authors reviewed and approved the final version of the manuscript and are accountable for all aspects of the research in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved.

Disclosure statement

R.B. received research support from BMS/Celgene and Takeda; and received honoraria and served on the advisory board for BMS, Taiho Oncology, and Takeda. K.W.L.Y. was a consultant for Astex, BMS/Celgene, F. Hoffmann La Roche, Novartis, Otsuka, Paladin, Pfizer, Shattuck Labs, Taiho Oncology, and Takeda; received research funding from Astex, Forma Therapeutics, F. Hoffmann La Roche, Genentech, Geron, Janssen, Jazz Pharmaceuticals, Medimmune, Novartis, Onconova, and Tolero; and received honoraria from AbbVie and Novartis. M.G. received research support (institutional clinical trial contract) from AbbVie, Amgen, BMS/Celgene, Geron, Gilead, Janssen, and Novartis and honoraria from BMS/Celgene; was an expert witness for Novartis and Taiho Oncology; and served on the advisory board for AbbVie, Amgen, BMS/Celgene, Jazz Pharmaceuticals, Novartis, Paladin, Pfizer, and Taiho Oncology. N.Z. received honoraria and served on the advisory board for BMS and Taiho Oncology. A.S. received honoraria and served on the advisory board for AbbVie, BMS, and Janssen; and received research funding from BMS. H.A.L. served on the advisory board and received honoraria and research funding from AbbVie, Alexion, AstraZeneca, BMS/Celgene, Janssen, Novartis, Taiho Oncology. V.B. received research support from the Canadian Institutes of Health Research and the Leukemia & Lymphoma Society of Canada and royalties or licenses from BioGene; was a consultant for AbbVie, AstraZeneca, and Janssen; and received honoraria from AbbVie, AstraZeneca, Janssen, Medicom, and Oncology Education. L.B. served on the advisory board and received honoraria from AbbVie, Alexion, Amgen, Astellas, Astex, BMS/Celgene, Janssen, Jazz Pharmaceuticals, Novartis, Otsuka, Paladin, Pfizer, Roche, and Treadwell; was a consultant and expert witness for AbbVie, Novartis, and Pfizer; and received travel/conference support from Novartis and Pfizer. E.S-H. served on the advisory board for BMS and Taiho Oncology. T.N. served on the advisory board and received speaker fees from BMS/Celgene. M-M.K. served on the advisory board for Celgene and Taiho Oncology; and received speaker fees from BMS. J.S. received research support from AbbVie, Astellas, BMS/Celgene, Novartis, Pfizer, and Taiho Oncology; served on the advisory board for AbbVie, Amgen, Astellas, BMS/Celgene, Jazz Pharmaceuticals, Novartis, Paladin, Pfizer, Taiho Oncology, and Teva; and is/was an investigator in clinical trials for AbbVie, Astellas, BMS/Celgene, Janssen, and Novartis. C.W. and D.T. are paid employees of BMS; D.T. is also a stockholder/shareholder of BMS. C.C. is a paid employee and a stockholder/shareholder of EVERSANA™, which was contracted by Celgene, a Bristol Myers Squibb Company, to work on this project. P.S. was a paid employee of EVERSANA™ at the time the study was conducted. G.C., L.C., L.M., D.K., N.F., R.D., A.P., A.T., M.S., and A.M. have no disclosures to report.

Data availability statement

The data that support the findings of this study are available in the supplementary material of this article and the data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was funded by Bristol Myers Squibb.