Use of Daratumumab in High Risk Multiple Myeloma: A Meta-analysis

Daratumumab is approved for use in newly diagnosed and relapsed/refractory multiple myeloma (MM), however the patients most likely to benefit from its addition to standard anti-myeloma therapy is unclear. This meta-analysis included 2340 newly diagnosed MM patients (1982 with standard risk and 358 with high risk cytogenetics) and 673 patients with relapsed/refractory MM (513 with standard risk and 160 with high risk cytogenetics) to assess which cytogenetic subgroups derived PFS benefit from Daratumumab. Studies included were the CASSIOPEIA, MAIA and ALCYONE (for newly diagnosed MM) and the CASTOR and POLLUX trials (for relapsed/refractory MM). Daratumumab's addition led to a clear benefit in standard risk newly diagnosed MM (HR 0.43; 95% CI, 0.35-0.53;  < .05) and both high and standard risk relapsed/refractory disease (HR 0.28; 95% CI, 0.21-0.36;  < .05 and HR 0.48; 95% CI, 0.30-0.76;  < .05, respectively). No clear benefit was seen in newly diagnosed high risk MM. These findings fail to demonstrate PFS benefit from Daratumumab's addition in high risk newly diagnosed MM. Data forthcoming from the GRIFFIN and MASTER trials may increase the power of the study and provide a definitive answer. Daratumumab remains important in standard risk upfront and relapsed/refractory MM and high risk relapsed/refractory MM.