Sex Differences in Multiple Myeloma Biology but not Clinical Outcomes: Results from 3894 Patients in the Myeloma XI Trial.


Journal

Clinical lymphoma, myeloma & leukemia
ISSN: 2152-2669
Titre abrégé: Clin Lymphoma Myeloma Leuk
Pays: United States
ID NLM: 101525386

Informations de publication

Date de publication:
10 2021
Historique:
received: 30 11 2020
accepted: 16 04 2021
pubmed: 2 6 2021
medline: 9 2 2022
entrez: 1 6 2021
Statut: ppublish

Résumé

Sex differences in the incidence and outcomes of several cancers are well established. Multiple myeloma (MM) is a malignant plasma cell dyscrasia accounting for 2% of all new cancer cases in the UK. There is a clear sex disparity in MM incidence, with 57% of cases in males and 43% in females. The mechanisms behind this are not well understood and the impact of sex on patient outcomes has not been thoroughly explored. We investigated the association of sex with baseline disease characteristics and outcome in 3894 patients recruited to the phase III UK NCRI Myeloma XI trial, in which treatment exposure to lenalidomide predominated. Females were significantly more likely to have the molecular lesions t(14;16) and del(17p) and were more likely to meet the cytogenetic classification of high-risk (HiR) or ultra-high-risk disease (UHiR). There was no difference in progression-free survival (PFS) or overall survival (OS) between the sexes in the overall population. Our data suggest that the genetic lesions involved in the initiation and progression of MM may be different between the sexes. Although females were more likely to have the poor prognosis lesions t(14;16) and del(17p), and were more likely to be assessed as having HiR or UHiR disease, this was not associated with reduced PFS or OS. In female patients the trial treatment may have been able to overcome some of the adverse effects of high-risk cytogenetic lesions. MicroAbstract Multiple myeloma (MM) is more common in males compared to females but the reasons behind this are not well understood and the impact of sex on patient outcomes is unclear. This study demonstrates fundamental differences in genetic lesions underlying the biology of MM between males and females. However, we found that progression-free survival and overall survival were the same in both sexes.

Sections du résumé

BACKGROUND
Sex differences in the incidence and outcomes of several cancers are well established. Multiple myeloma (MM) is a malignant plasma cell dyscrasia accounting for 2% of all new cancer cases in the UK. There is a clear sex disparity in MM incidence, with 57% of cases in males and 43% in females. The mechanisms behind this are not well understood and the impact of sex on patient outcomes has not been thoroughly explored.
PATIENTS AND METHODS
We investigated the association of sex with baseline disease characteristics and outcome in 3894 patients recruited to the phase III UK NCRI Myeloma XI trial, in which treatment exposure to lenalidomide predominated.
RESULTS
Females were significantly more likely to have the molecular lesions t(14;16) and del(17p) and were more likely to meet the cytogenetic classification of high-risk (HiR) or ultra-high-risk disease (UHiR). There was no difference in progression-free survival (PFS) or overall survival (OS) between the sexes in the overall population.
CONCLUSION
Our data suggest that the genetic lesions involved in the initiation and progression of MM may be different between the sexes. Although females were more likely to have the poor prognosis lesions t(14;16) and del(17p), and were more likely to be assessed as having HiR or UHiR disease, this was not associated with reduced PFS or OS. In female patients the trial treatment may have been able to overcome some of the adverse effects of high-risk cytogenetic lesions. MicroAbstract Multiple myeloma (MM) is more common in males compared to females but the reasons behind this are not well understood and the impact of sex on patient outcomes is unclear. This study demonstrates fundamental differences in genetic lesions underlying the biology of MM between males and females. However, we found that progression-free survival and overall survival were the same in both sexes.

Identifiants

pubmed: 34059488
pii: S2152-2650(21)00157-9
doi: 10.1016/j.clml.2021.04.013
pmc: PMC8528179
pii:
doi:

Types de publication

Clinical Trial, Phase III Journal Article Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

667-675

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Sarah Bird (S)

The Institute of Cancer Research, London; The Royal Marsden Hospital, London.

David Cairns (D)

Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds.

Tom Menzies (T)

Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds.

Kevin Boyd (K)

The Institute of Cancer Research, London; The Royal Marsden Hospital, London.

Faith Davies (F)

Perlmutter Cancer Center, NY Langone Health, New York, USA.

Gordon Cook (G)

Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds.

Mark Drayson (M)

Clinical Immunology, University of Birmingham, Birmingham.

Walter Gregory (W)

Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds.

Matthew Jenner (M)

University Hospital Southampton NHS Foundation Trust, Southampton.

John Jones (J)

The Institute of Cancer Research, London.

Martin Kaiser (M)

The Institute of Cancer Research, London; The Royal Marsden Hospital, London.

Roger Owen (R)

St James's University Hospital, Leeds.

Graham Jackson (G)

Department of Haematology, Newcastle University, Newcastle.

Gareth Morgan (G)

Perlmutter Cancer Center, NY Langone Health, New York, USA.

Charlotte Pawlyn (C)

The Institute of Cancer Research, London; The Royal Marsden Hospital, London. Electronic address: charlotte.pawlyn@icr.ac.uk.

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