Daratumumab plus lenalidomide and dexamethasone <i>versus</i> lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX

In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly reduced risk of progression/death <i>versus</i> lenalidomide/dexamethasone alone in relapsed/refractory multiple myeloma. We provide one additional year of follow up and include the effect on minimal residual disease and in clinically relevant subgroups. After 25.4 months of follow up, daratumumab plus lenalidomide/dexamethasone prolonged progression-free survival <i>versus</i> lenalidomide/dexamethasone alone (median not reached <i>vs</i> 17.5 months; hazard ratio, 0.41; 95% confidence interval, 0.31-0.53; <i>P</i><0.0001). The overall response rate was 92.9% <i>versus</i> 76.4%, and 51.2% <i>versus</i> 21.0% achieved a complete response or better, respectively (both <i>P</i><0.0001). At the 10^-5 sensitivity threshold, 26.2% <i>versus</i> 6.4% were minimal residual disease-negative, respectively (<i>P</i><0.0001). <i>Post hoc</i> analyses of clinically relevant patient subgroups demonstrated that progression-free survival was significantly prolonged for daratumumab plus lenalidomide/dexamethasone <i>versus</i> lenalidomide/dexamethasone regardless of number of prior lines of therapy. Patients previously treated with lenalidomide or thalidomide and those refractory to bortezomib received similar benefits (all <i>P</i><0.01). Treatment benefit with daratumumab plus lenalidomide/dexamethasone was maintained in high-risk patients (median progression-free survival 22.6 <i>vs</i> 10.2 months; hazard ratio, 0.53; 95% confidence interval, 0.25-1.13; <i>P</i>=0.0921) and patients with treatment-free intervals of >12 and ≤12 months and >6 and ≤6 months. No new safety signals were observed. In relapsed/refractory multiple myeloma patients, daratumumab plus lenalidomide/dexamethasone continued to improve progression-free survival and deepen responses <i>versus</i> lenalidomide/dexamethasone. Trial Registration: <i>clinicaltrials.gov identifier: 02076009</i>.