Myelodysplastic syndrome

An MDS-specific frailty index based on cumulative deficits adds independent prognostic information to clinical prognostic scoring

Abstract

The frailty index (FI) is based on the principle that the more deficits an individual has, the greater their risk of adverse outcomes. It is expressed as a ratio of the number of deficits present to the total number of deficits considered. We developed an MDS-specific FI using a prospective MDS registry and assessed its ability to add prognostic power to conventional prognostic scores in MDS. The 42 deficits included in this FI included measurements of physical performance, comorbidities, laboratory values, instrumental activities of daily living, quality of life and performance status. Of 644 patients, 440 were eligible for FI calculation. The median FI score was 0.25 (range 0.05–0.67), correlated with age and IPSS/IPSS-R risk scores and discriminated overall survival. With a follow-up of 20 months, survival was 27 months (95% CI 24–30.4). By multivariate analysis, age >70, FI, transfusion dependence, and IPSS were significant covariates associated with OS. The incremental discrimination improvement of the frailty index was 37%. We derived a prognostic score with five risk groups and distinct survivals ranging from 7.4 months to not yet reached. If externally validated, the MDS-FI could be used as a tool to refine the risk stratification of current clinical prognostication models.

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Fig. 1: FI is not normally distributed.
Fig. 2: Kaplan−Meier survival curve for three FI cut points (n = 440).
Fig. 3
Fig. 4: Kaplan−Meier OS curves by composite risk score.

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Acknowledgements

The authors thank Celgene Canada and Crashley estate for national MDS financial support.

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Correspondence to R. Buckstein.

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The national Canadian registry is financially supported by Celgene and Otsuka. RA.: Sponsored talks—Alexion. MMK: Consultant—Seattle Genetics (brentuximab vedotin), Honoraria—Novartis, Scientific Advisory Board—Janssen, Shire, Hoffman-La Roche, Sanofi Genzyme, Celgene. BL: Medical advisory boards and Speaker Bureau—Celgene, Pfizer, Novartis, AMGEN, Astellas, Otsuka, Jazz, Abbvie. MS: Advisory boards—Jazz, Pfizer, Novartis, Astellas, Celgene. HAL: Advisory boards, honoraria, research funding—Abbvie, Alexion, Celgene, Novartis, Advisory boards, honoraria—Otsuka. ESt-H: Advisory boards—BMS, Amgen, Celgene, Teva, Novartis, Speaker honoratrium—BMS, Sanofi, Novartis. NF: Research support—Boehringer Ingelheim, Roche, Pfizer, Merck, Honoraria—Roche, Novartis, Bristol Myers Squibb, Celgene, Pfizer, Scientific Advisory Board—Novartis, Pfizer, Lundbeck, Celgene, Janssen, Sanofi, Alexion, Roche, Ipsen, Takeda, Merck, Amgen, Bristol Myers Squibb, Astra Zeneca. AS: Advisory boards: Amgen, Janssen, Abbvie, Celgene, Sponsored talks—Janssen. KY: Research funding—Astex, Hoffman La Roche, MedImmune, Merck, Millenium, Roche/Genentech, Honoraria—Novartis, Pfizer, Board of Directors or advisory committees: Astellas, Celgene, Novartis, Pfizer, Takeda. JS: Advisory boards—Celgene, Novartis, Pfizer, Astellas, Abbvie, Amgen, speaking fees—Teva, Celgene, travel support—Pfizer. TN: Ad boards and Sponsored talks—Celgene, Alexion, Novartis, Ad boards—Paladin Labs, Otsuka. VB: Industry Research Funding—Gilead, Janssen, Roche, Ad boards—Abbvie, Astra Zeneca, Janssen, Gilead, Roche, Sponsored talk -CAPhO Abbvie, Academic Research Support—CIHR, LLSC, Research Manitoba and CancerCare Manitoba Foundation, Licensing Fees—BIOGEN and The Dana-Farber Cancer Institute. RB: Research funding support and honoraria for advisory board panels—Celgene, Research funding support—Otsuka. All other authors: no disclosures.

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Starkman, R., Alibhai, S., Wells, R.A. et al. An MDS-specific frailty index based on cumulative deficits adds independent prognostic information to clinical prognostic scoring. Leukemia 34, 1394–1406 (2020). https://doi.org/10.1038/s41375-019-0666-7

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