Phase 2 trial of induction and extended consolidation with daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone for high-risk multiple myeloma: 5-year follow-up

High-risk multiple myeloma (MM), defined by two or moren high-risk cytogenetic abnormalities (HRCAs), high-risk gene expression profilig (GEP), or plasma cell leukemia, is associated with poor long-term outcomes. The phase 2 OPTIMUM trial, at 22 centers in the UK, showed that intensified induction, extended consolidation, and maintenance after autologous stem-cell transplantation (ASCT) improved progression-free survival (PFS) for patients with high-risk MM. Five-year follow-up of survival outcomes from OPTIMUM have now been published. The analysis included 107 patients with newly diagnosed high-risk MM who received induction and extended consolidation with daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone, with 120 genetically matched patients from the Myeloma XI trial as external control. Median follow-up was 71.1 months for OPTIMUM and 117.8 months for Myeloma XI. The figure shows survival outcomes. Median PFS (not reached versus 24.4 months; HR 0.32; p<0.0001) and overall survival (not reached versus 57.4 months; HR 0.43; p<0.0001) were longer in OPTIMUM than in Myeloma XI. Median PFS2 was not reached in OPTIMUM and 43.9 months in Myeloma XI (HR 0.26; p<0.0001). The survival benefit was consistent across high-risk MM subgroups, except for patients with three or more HRCAs. The authors conclude that OPTIMUM shows sustained PFS and OS improvement with risk-stratified extended therapy, supporting implementation of molecular diagnostics and tailored treatment in patients with newly diagnosed high-risk MM.