Co-Occurrence of Cytogenetic Abnormalities and High-Risk Disease in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma
Year: 2025
Type: article
Study designs: Systematic Review, Meta-Analysis
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.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco-24-01253
Authors: Martin F. Kaiser, Pieter Sonneveld, David A. Cairns, Marc S. Raab, Jesús San-Miguel Izquierdo, Rick Zhang, Jorge Acosta, Alessandra Larocca, Rakesh Popat, Cong Li, Marc-A. Baertsch, Sarah R. Brown, JuanJose Lahuerta Palacios, Anita K. Gandhi, Sandrine Macé, Pellegrino Musto, Kwee Yong, Elias K. Mai, Franck Dubin, Joan Blade, Andrea Capra, Gordon Cook, Uta Bertsch, María-Victoria Mateos, Mario Boccadoro, Graham H. Jackson, Norma C. Gutiérrez, Francesca Gay, Niels Weinhold
Institutions: Royal Marsden NHS Foundation Trust, Institute of Cancer Research, Royal Marsden Hospital, Erasmus MC, University of Leeds, Heidelberg University, University Hospital Heidelberg, Clinica Universidad de Navarra, Bristol-Myers Squibb (Switzerland), University of Turin, University College London, Takeda (United States), Research Institute Hospital 12 de Octubre, Hospital Universitario 12 De Octubre, Bristol-Myers Squibb (United States), Sanofi (France), University of Bari Aldo Moro, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, St James's University Hospital, Universidad de Salamanca, Newcastle University, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer, Centro de Investigación Biomédica en Red de Cáncer, Instituto de Biología Molecular y Celular del Cáncer de Salamanca, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4407680750