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Multiple myeloma gammopathies

Bone marrow plasma cells 20% or greater discriminate presentation, response, and survival in AL amyloidosis

A Correction to this article was published on 29 July 2020

This article has been updated

Abstract

We explored the association between bone marrow plasma cells (BMPCs) and disease presentation and outcome among 1574 AL patients. Three BMPC groups were formulated: <5% (n = 231, 15% of study population), 5–19% (n = 1045, 66%), and ≥20% (n = 298, 19%). Heart and renal involvement were more and less prevalent, respectively, with increasing BMPCs. Patients with ≥20% BMPCs had higher likelihood for classic myeloma phenotype with less skewed lambda restriction, a higher rate of intact immunoglobulin secretion, a lower hemoglobin and higher rates of hypercalcemia and bone lytic lesions. High-risk cytogenetic abnormalities were more common in ≥20% BMPCs. Complete hematological response was less frequent with rising BMPCs. The median survival was inversely associated with the BMPC groups (81, 33, 12 months for <5%, 5–19%, and ≥20% BMPCs, respectively; P < 0.001). Survival discrimination was maintained at 1-year landmark and in those who achieved a complete response. Multivariate analysis accounting for known prognostic markers yielded an independent prognostic role for ≥20% BMPCs, but not for the other BMPC groups. AL patients with 20% or greater BMPCs have poorer outcome independent of their cardiac risk category and stem cell transplant eligibility. Distinct interventions in these patients should be explored to improve outcome.

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Acknowledgements

The study was supported in part by the Jabbs Foundation (Birmingham, United Kingdom), the Henry J. Predolin Foundation (USA), and National Institutes of Health National Cancer Institute grant P50 CA186781.

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Authors and Affiliations

Authors

Contributions

EM designed the study, collected the data, analyzed the data, wrote the first draft and approved the final version of the manuscript; MAG, TVK, SS, RSG, MQL, FKB, DD, SRH, PK, NL, AF, MH, YLH, WG, RW, SR, JAL, YL, SZ, SVR, SKK, revised the manuscript critically and approved the final version of the manuscript. RAK Performed patients’ follow-up, revised the manuscript critically and approved  the final version of the manuscript; AD designed the study, analyzed the data, wrote the first draft and approved the final version of the manuscript.

Corresponding author

Correspondence to Eli Muchtar.

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Conflict of interest

EM: None; MAG: Consultancy (Milleniu) and honoraria (Celgene, Millenium, Onyx, Novartis, Smith Kline, Prothena, Ionis). TVK: None; SS: None; RSG: None; MQL: Research funding (Celgene); FB: None; DD: Research funding (Karyopharm Therapeutics, Amgen, and Millenium Pharmaceuticals); SRH: None; PK: Research funding (Takeda, Celgene, and Amgen); NL: None; AF: None; MH: None; YLH: None; WG: None; RW: None; SR: None; JAL: None; YL: None; SZ: None; SVR: None; RAK: None; SKK: Consultancy (Celgene, Millennium, Onyx, Janssen, and BMS); and research funding (Celgene, Millennium, Novartis, Onyx AbbVie, Janssen, and BMS). AD: Research funding (Celgene, Millennium, Pfizer, and Janssen), Travel grant (Pfizer).

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Muchtar, E., Gertz, M.A., Kourelis, T.V. et al. Bone marrow plasma cells 20% or greater discriminate presentation, response, and survival in AL amyloidosis. Leukemia 34, 1135–1143 (2020). https://doi.org/10.1038/s41375-019-0655-x

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