A phase 3 trial evaluated the efficacy and safety of daratumumab in combination with lenalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma. The study enrolled 569 patients who had received one or more previous lines of therapy. Patients were randomly assigned to either the daratumumab group (daratumumab, lenalidomide, and dexamethasone) or the control group (lenalidomide and dexamethasone). The primary endpoint was progression-free survival (PFS). At a median follow-up of 13.5 months, the daratumumab group had a significantly lower risk of disease progression or death compared to the control group (hazard ratio, 0.37; 95% CI, 0.27 to 0.52; P<0.001). The 12-month PFS rate was 83.2% in the daratumumab group versus 60.1% in the control group. The median PFS was not reached in the daratumumab group, compared to 18.4 months in the control group. The overall response rate was significantly higher in the daratumumab group (92.9% vs. 76.4%). The rate of complete response or better was also significantly higher in the daratumumab group (43.1% vs. 19.2%). Additionally, the daratumumab group had a significantly higher rate of results below the threshold for minimal residual disease (22.4% vs. 4.6%). Common adverse events in the daratumumab group included neutropenia (51.9%), thrombocytopenia (12.7%), and anemia (12.4%). Daratumumab-associated infusion-related reactions occurred in 47.7% of patients, mostly of grade 1 or 2. The addition of daratumumab to lenalidomide and dexamethasone significantly prolonged PFS and improved overall response rates, although it was associated with higher rates of neutropenia and infusion-related reactions compared to the control therapy. The study was funded by Janssen Research and Development. The results showed that daratumumab in combination with lenalidomide and dexamethasone significantly improved outcomes in patients with relapsed or refractory multiple myeloma.A phase 3 trial evaluated the efficacy and safety of daratumumab in combination with lenalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma. The study enrolled 569 patients who had received one or more previous lines of therapy. Patients were randomly assigned to either the daratumumab group (daratumumab, lenalidomide, and dexamethasone) or the control group (lenalidomide and dexamethasone). The primary endpoint was progression-free survival (PFS). At a median follow-up of 13.5 months, the daratumumab group had a significantly lower risk of disease progression or death compared to the control group (hazard ratio, 0.37; 95% CI, 0.27 to 0.52; P<0.001). The 12-month PFS rate was 83.2% in the daratumumab group versus 60.1% in the control group. The median PFS was not reached in the daratumumab group, compared to 18.4 months in the control group. The overall response rate was significantly higher in the daratumumab group (92.9% vs. 76.4%). The rate of complete response or better was also significantly higher in the daratumumab group (43.1% vs. 19.2%). Additionally, the daratumumab group had a significantly higher rate of results below the threshold for minimal residual disease (22.4% vs. 4.6%). Common adverse events in the daratumumab group included neutropenia (51.9%), thrombocytopenia (12.7%), and anemia (12.4%). Daratumumab-associated infusion-related reactions occurred in 47.7% of patients, mostly of grade 1 or 2. The addition of daratumumab to lenalidomide and dexamethasone significantly prolonged PFS and improved overall response rates, although it was associated with higher rates of neutropenia and infusion-related reactions compared to the control therapy. The study was funded by Janssen Research and Development. The results showed that daratumumab in combination with lenalidomide and dexamethasone significantly improved outcomes in patients with relapsed or refractory multiple myeloma.