Response adaptive salvage treatment with daratumumab–lenalidomide–dexamethasone for newly diagnosed transplant‐eligible multiple myeloma patients failing front‐line bortezomib‐based induction therapy—ALLG MM21

Summary In Australia, bortezomib‐based induction (V‐IND) is used in >90% of newly diagnosed transplant‐eligible multiple myeloma (MM) patients. Four cycles of V‐IND with bortezomib–cyclophosphamide–dexamethasone or bortezomib–lenalidomide–dexamethasone are available via the Pharmaceutical Benefits Scheme prior to autologous stem cell transplantation (ASCT). Patients who demonstrate suboptimal response or who are refractory to V‐IND demonstrate inferior survival, representing a subgroup of MM where an unmet need persists. We evaluated an early, response‐adapted approach in these patients by switching to an intensive sequential therapeutic strategy incorporating daratumumab–lenalidomide–dexamethasone‐based (DRd) salvage, high‐dose melphalan ASCT followed by DRd consolidation and R maintenance. The overall response rate following four cycles of DRd salvage was 72% (95% credible interval: 57.9–82.4); prespecified, dual, Bayesian proof‐of‐concept criteria were met. Euro‐flow minimal residual disease (MRD) negativity was 46% in the intention‐to‐treat population and 79% in the evaluable population following 12 cycles of DRd consolidation. At the 24‐month follow‐up, median progression‐free survival and overall survival were not reached. DRd salvage was well tolerated with grade 3 and 4 events reported in 24% and 8% respectively. Response‐adapted DRd combined with ASCT achieves high rates of MRD negativity and durable disease control in this functional high‐risk group.