Kaiser, M.F. orcid.org/0000-0002-3677-4804, Sonneveld, P. orcid.org/0000-0002-0808-2237, Cairns, D.A. orcid.org/0000-0002-2338-0179 et al. (26 more authors) (2025) Co-Occurrence of Cytogenetic Abnormalities and High-Risk Disease in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma. Journal of Clinical Oncology. ISSN 0732-183X
Abstract
Purpose Survival 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. Methods A 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. Results Twenty-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. Conclusion The 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 by American Society of Clinical Oncology. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Clinical Trials Research (LICTR) (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 Feb 2025 10:21 |
Last Modified: | 24 Feb 2025 10:21 |
Status: | Published online |
Publisher: | American Society of Clinical Oncology |
Identification Number: | 10.1200/jco-24-01253 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:223673 |