Efficacy and safety of daratumumab for the treatment of multiple myeloma: a series of Cochrane reviews

Introduction: Daratumumab has approved indications for the treatment of patients with newly diagnosed multiple myeloma (NDMM) both eligible and ineligible for transplant and treatment of relapsed or refractory multiple myeloma (RRMM). The aim was to evaluate the efficacy and safety of daratumumab for transplant-ineligible NDMM patients (PICO 1), transplant eligible NDMM patients (PICO 2) and for RRMM patients (PICO 3). Methods: For each PICO we conduct one Cochrane review according to the standard methodology as outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and assess the certainty in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Our prioritised outcomes were overall survival, adverse events (CTCAE grade ≥3) and quality of life. Results: Transplant-ineligible NDMM: We identified two RCTs (MAIA, ALCYONE) reporting on 1443 patients. Treatment with daratumumab probably increases overall survival (HR 0.67, 95% CI 0.5 to 0.85, I2 39%, moderate-certainty evidence), results in a slight increase of adverse events (grade ≥3) (RR 1.05, 95% CI 1.0 to 1.11, I2 26%, high-certainty evidence), more people probably gain at least 10 points of global health status after start of treatment when compared to people receiving no daratumumab (RR 1.13, 95% CI 1.13 to 1.23, I2 0%, moderate-certainty evidence). Transplant-ineligible NDMM: We identified two RCTs (CASSIOPEIA, GRIFFIN) reporting on 1292 patients. GRIFFIN included 207 patients, but did not report any of our crucial outcomes. Treatment with daratumumab may increase overall survival (HR 0.52, 95% CI 0.33 to 0.82, low-certainty evidence), results in a slight increase of adverse events (grade ≥3) (RR 1.06, 95% CI 1.0 to 1.13, high-certainty evidence), more people may gain at least 10 points of global health status after start of treatment compared to people receiving no daratumumab (RR 1.07, 95% CI 0.91 to 1.24, low-certainty evidence) at 9.0 months after start of treatment. RRMM: We identified four RCTs (CANDOR, CASTOR, LEPUS, POLLUX) reporting on 1717 patients. Treatment with daratumumab probably increases overall survival (HR 0.62, 95% CI 0.49 to 0.79, I2 7%, moderate-certainty evidence). We were able to include safety data from two trials (CASTOR, POLLUX) for 1044 patients. Treatment with daratumumab probably results in a slight increase of adverse events (grade ≥3) (RR 1.17, 95% CI 1.04 to 1.31, I2 64%, moderate-certainty evidence) and more people may gain at least 10 points of global health status after start of treatment compared to people receiving no daratumumab (RR 1.07, 95% CI 1.07 to 1.22, I2 0%, low-certainty evidence) at 9 months after start of treatment. Conclusions: Treatment with daratumumab is likely to retrieve gain in survival, increases the risk of adverse events (grade ≥3) and may contribute to a clinically important improvement of quality of life. EA – previously submitted to EHA 2021. Keywords: Multiple Myeloma No conflicts of interests pertinent to the abstract.