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Lookup NU author(s): Professor Graham Jackson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 by American Society of Clinical Oncology.PURPOSESurvival for patients with multiple myeloma (MM) has improved but outcomes remain heterogeneous. Consistent diagnostic identification of high-risk disease is desirable to address unmet patient need. The aim was to investigate the consistency of association of co-occurrence of high-risk cytogenetic abnormalities (HRCAs) with prognosis in patients with newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM), and across a range of treatment modalities. METHODSA systematic review of randomized controlled trials of MM that reported testing for HRCA between January 1, 2000, and December 9, 2021, was performed. Groups were contacted and asked to locally perform a novel, federated analysis of their data for single hit (one HRCA) and double hit (≥two HRCAs), using a centrally provided algorithm. Analysis results were centrally collated and meta-analyzed to assess the hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) for one/≥two HRCAs across patient subgroups using random-effects models.RESULTSTwenty-four trials including 13,926 patients were included. The median age of participants was 66.5 years (IQR, 59-72) and 56.5% were male (IQR, 52-60). The HR for PFS was 2.28 (95% CI, 2.05 to 2.54) for patients with ≥two HRCAs and 1.51 (95% CI, 1.38 to 1.65) for patients with one HRCA. The HR for OS was 2.94 (95% CI, 2.49 to 3.47) and 1.69 (95% CI, 1.52 to 1.88) for the two subgroups, respectively. In studies initiated since 2015, the effect abides (≥two HRCA PFS, HR, 2.39 [95% CI, 1.96 to 2.91]; OS, 3.10 [95% CI, 2.10 to 4.60]) both for NDMM and RRMM. Heterogeneity related to transplant eligibility and relapsed/refractory status was as expected.CONCLUSIONThe association of ≥two HRCAs with the poorest outcome in NDMM and RRMM, and across treatment modalities, as demonstrated here for the first time to our knowledge, allows for more focused development of novel approaches to these patients with high unmet need.
Author(s): Kaiser MF, Sonneveld P, Cairns DA, Raab MS, San-Miguel Izquierdo J, Zhang R, Acosta J, Larocca A, Popat R, Li C, Baertsch M-A, Brown SR, Lahuerta Palacios J, Gandhi AK, Mace S, Musto P, Yong K, Mai EK, Dubin F, Blade J, Capra A, Cook G, Bertsch U, Mateos M-V, Boccadoro M, Jackson GH, Gutierrez NC, Gay F, Weinhold N
Publication type: Article
Publication status: Published
Journal: Journal of Clinical Oncology
Year: 2025
Pages: epub ahead of print
Online publication date: 18/02/2025
Acceptance date: 14/01/2025
Date deposited: 10/03/2025
ISSN (print): 0732-183X
ISSN (electronic): 1527-7755
Publisher: Lippincott Williams and Wilkins
URL: https://doi.org/10.1200/JCO-24-01253
DOI: 10.1200/JCO-24-01253
Data Access Statement: All data included in this manuscript are available in tables, figures, and the Data Supplement. Code used to undertake this analysis is available from the authors upon request.
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