BACKGROUND High-dose chemotherapy with autologous stem cell transplantation has been the standard treatment for young patients with newly diagnosed myeloma. However, promising emerging data with the combination of lenalidomide, bortezomib and dexamethasone (RVD) have raised questions about the role of transplantation. METHODS We randomly assigned 700 patients to the RVD group (eight cycles; 350 patients) or to the transplant group (three cycles of RVD, followed by high-dose melphalan plus stem cell transplantation, followed by two additional cycles of RVD; 350 patients). Patients in both arms received maintenance lenalidomide for 1 year. The primary end point was progression-free survival. RESULTS Progression-free survival was significantly longer in the transplant versus the RVD group (median, 50 months vs. 36 months; hazard ratio, 0.65; P<0.001). This benefit was observed across all patient subgroups, including those stratified by International Staging System stage and cytogenetic risk profile. Transplantation versus RVD alone was associated with increased complete response (59% vs. 48%; P=0.006), and minimal residual disease negativity (79% vs. 65%; P<0.001). Overall survival was similar in both arms (4-year survival, 81% in the transplant group vs. 82% in the RVD group). Grade 3 or 4 neutropenia was significantly more common with transplantation than with RVD (92% vs. 47%), as were gastrointestinal adverse events (28% vs. 7%) and infections (20% vs. 9%). Rates of treatment-related deaths, second primary malignancies, thromboembolic events, and peripheral neuropathy were similar in the two treatment groups. CONCLUSIONS RVD plus transplant significantly prolonged progression-free survival as compared with RVD alone without overall survival difference.

No abstract

No abstract

BACKGROUNDLenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population. METHODSWe randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival. RESULTSAt a median follow-up of 28.0 months, disease progression or death had occurred in 240 patients (97 of 368 patients [26.4%] in the daratumumab group and 143 of 369 patients [38.8%] in the control group). The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P<0.001). The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P<0.001). A total of 24.2% of the patients in the daratumumab group, as compared with 7.3% of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 10 5 white cells) (P<0.001). The most common adverse events of grade 3 or 4 were neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%). CONCLUSIONSAmong patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among those who received lenalidomide and dexamethasone alone. A higher incidence of neutropenia and pneumonia was observed in the daratumumab group. (Funded by Janssen Research and Development; MAIA ClinicalTrials.gov number, NCT02252172.