MULTIPLE myeloma patients with two or more high-risk cytogenetic abnormalities (HRCA) have significantly poorer outcomes compared to those with one or no HRCAs, regardless of disease stage or treatment modality.
A systematic review and meta-analysis of 24 randomised controlled trials involving 13,926 multiple myeloma patients was conducted to investigate the prognostic impact of co-occurring HRCAs. The study included trials from January 2000 to December 2021, with a median participant age of 66.5 years and 56.5% male representation. A novel federated analysis approach was employed to assess the hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) in patients with single hit (one HRCA) and double hit (≥2 HRCAs) across various subgroups.
The results revealed striking differences in outcomes based on the number of HRCAs. Patients with ≥2 HRCAs had a HR for PFS of 2.28 (95% CI: 2.05–2.54) and for OS of 2.94 (95% CI: 2.49–3.47). In contrast, those with one HRCA showed HRs of 1.51 (95% CI: 1.38–1.65) for PFS and 1.69 (95% CI: 1.52–1.88) for OS. Notably, this trend persisted in more recent studies initiated since 2015, with ≥2 HRCAs associated with HRs of 2.39 for PFS and 3.10 for OS. The findings were consistent across newly diagnosed and relapsed/refractory multiple myeloma patients, as well as various treatment modalities.
This study provides compelling evidence for the first time that the presence of ≥2 HRCAs consistently identifies patients with the poorest outcomes in multiple myeloma. These findings have significant implications for clinical practice, suggesting that patients with multiple HRCAs should be considered for more aggressive treatment strategies or novel therapeutic approaches.
Jenna Lorge, EMJ
Reference
Kaiser MF et al. Co-occurrence of cytogenetic abnormalities and high-risk disease in newly diagnosed and relapsed/refractory multiple myeloma. JCO.2025;DOI:10.1200/JCO-24-01253.
