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Characterisation of immunoparesis in newly diagnosed myeloma and its impact on progression-free and overall survival in both old and recent myeloma trials

Lookup NU author(s): Professor Graham Jackson

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2018 The Author(s) We measured immunosuppression at myeloma diagnosis and assessed the impact on survival in 5826 UK myeloma trial patients. Polyclonal immunoglobulin levels were below normal in 85% of patients and above normal in only 0.4% of cases for IgA, 0.2% for IgM and no cases for IgG. Immunoparesis had a greater impact in recent trials: median overall survival (OS) was up to 3 years longer for patients without immunoparesis compared to the old trials, less than 1 year longer. Median progression-free survival (PFS) was 39%, 36% and 57% longer for patients with normal IgG, IgA and IgM levels, respectively. The depth of IgM suppression, but not the depth of IgG or IgA suppression, was prognostic for survival: the most severely suppressed IgM tertile of patients OS was 0.9 years shorter than those in the top tertile, and 2.6 years shorter than OS of those with normal IgM levels (p = .007). The degree of suppression of polyclonal IgM levels below normal was associated with worse PFS (p = .0002). Infection does not appear to be the main mechanism through which immunoparesis affects survival. We hypothesise that IgM immunoparesis impacts through a combination of being associated with more aggressive disease and reduced immune surveillance against relapse.


Publication metadata

Author(s): Heaney JLJ, Campbell JP, Iqbal G, Cairns D, Richter A, Child JA, Gregory W, Jackson G, Kaiser M, Owen R, Davies F, Morgan G, Dunn J, Drayson MT

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2018

Volume: 32

Pages: 1727-1738

Print publication date: 01/08/2018

Online publication date: 20/06/2018

Acceptance date: 27/04/2018

Date deposited: 02/07/2018

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41375-018-0163-4

DOI: 10.1038/s41375-018-0163-4


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