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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

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 great...

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Autores principales: Heaney, Jennifer L. J., Campbell, John P., Iqbal, Gulnaz, Cairns, David, Richter, Alex, Child, J. Anthony, Gregory, Walter, Jackson, Graham, Kaiser, Martin, Owen, Roger, Davies, Faith, Morgan, Gareth, Dunn, Janet, Drayson, Mark T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087716/
https://www.ncbi.nlm.nih.gov/pubmed/29925902
http://dx.doi.org/10.1038/s41375-018-0163-4
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author Heaney, Jennifer L. J.
Campbell, John P.
Iqbal, Gulnaz
Cairns, David
Richter, Alex
Child, J. Anthony
Gregory, Walter
Jackson, Graham
Kaiser, Martin
Owen, Roger
Davies, Faith
Morgan, Gareth
Dunn, Janet
Drayson, Mark T.
author_facet Heaney, Jennifer L. J.
Campbell, John P.
Iqbal, Gulnaz
Cairns, David
Richter, Alex
Child, J. Anthony
Gregory, Walter
Jackson, Graham
Kaiser, Martin
Owen, Roger
Davies, Faith
Morgan, Gareth
Dunn, Janet
Drayson, Mark T.
author_sort Heaney, Jennifer L. J.
collection PubMed
description 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.
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spelling pubmed-60877162018-08-14 Characterisation of immunoparesis in newly diagnosed myeloma and its impact on progression-free and overall survival in both old and recent myeloma trials Heaney, Jennifer L. J. Campbell, John P. Iqbal, Gulnaz Cairns, David Richter, Alex Child, J. Anthony Gregory, Walter Jackson, Graham Kaiser, Martin Owen, Roger Davies, Faith Morgan, Gareth Dunn, Janet Drayson, Mark T. Leukemia Article 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. Nature Publishing Group UK 2018-06-20 2018 /pmc/articles/PMC6087716/ /pubmed/29925902 http://dx.doi.org/10.1038/s41375-018-0163-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Heaney, Jennifer L. J.
Campbell, John P.
Iqbal, Gulnaz
Cairns, David
Richter, Alex
Child, J. Anthony
Gregory, Walter
Jackson, Graham
Kaiser, Martin
Owen, Roger
Davies, Faith
Morgan, Gareth
Dunn, Janet
Drayson, Mark T.
Characterisation of immunoparesis in newly diagnosed myeloma and its impact on progression-free and overall survival in both old and recent myeloma trials
title Characterisation of immunoparesis in newly diagnosed myeloma and its impact on progression-free and overall survival in both old and recent myeloma trials
title_full Characterisation of immunoparesis in newly diagnosed myeloma and its impact on progression-free and overall survival in both old and recent myeloma trials
title_fullStr Characterisation of immunoparesis in newly diagnosed myeloma and its impact on progression-free and overall survival in both old and recent myeloma trials
title_full_unstemmed Characterisation of immunoparesis in newly diagnosed myeloma and its impact on progression-free and overall survival in both old and recent myeloma trials
title_short Characterisation of immunoparesis in newly diagnosed myeloma and its impact on progression-free and overall survival in both old and recent myeloma trials
title_sort characterisation of immunoparesis in newly diagnosed myeloma and its impact on progression-free and overall survival in both old and recent myeloma trials
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087716/
https://www.ncbi.nlm.nih.gov/pubmed/29925902
http://dx.doi.org/10.1038/s41375-018-0163-4
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