Journal: British journal of haematology
Study focus
- The authors evaluated whether recently proposed 2025 International Myeloma Society/International Myeloma Working Group (IMS/IMWG) high-risk criteria remain valid in the era of quadruplet induction followed by autologous stem cell transplantation for newly diagnosed multiple myeloma.
Methods
- Retrospective cohort: 310 newly diagnosed patients treated uniformly with quadruplet therapy plus autologous transplant.
- Median follow-up: 41.5 months.
- Risk definitions compared: “Old” high-risk definition (t(4;14), t(14;16) or del(17p)) versus the new IMS/IMWG criteria, which integrate cytogenetics, next-generation sequencing–based features, β2-microglobulin, and renal function.
- Outcomes assessed: Associations with progression-free survival (PFS) and overall survival (OS), and comparison of model performance between old and new criteria.
Key findings
- High-risk prevalence: 29% (89/310) of patients met the new high-risk definition.
- Prognostic value of new high-risk status:
- PFS: HR 4.17 (95% CI 2.58–6.73; p<0.001).
- OS: HR 5.13 (95% CI 2.44–10.80; p<0.001).
- Model performance: The new criteria provided a better predictive model for both PFS and OS than the older cytogenetic-only definition.
- Risk reclassification: They reclassified some patients previously labeled as standard risk by legacy criteria, revealing a subset with markedly inferior outcomes despite modern quadruplet-plus-ASCT therapy.
Clinical implication
- In patients receiving contemporary induction and transplant, the 2025 IMS/IMWG high-risk criteria more accurately identify individuals at high risk of early progression and death than older cytogenetic-based systems, supporting their adoption for risk stratification, clinical trial design, and treatment intensification strategies.