Daratumumab added to standard of care in patients with newly diagnosed multiple myeloma: A network meta-analysis

Purpose To investigate the activity and safety of daratumumab added to standard of care and evaluate the relative efficacy of DRd vs DVMP and other regimens on survival endpoints for untreated myeloma, we undertook this meta-analysis. Methods We searched published reports that described the activity and safety of daratumumab added to standard of care for untreated myeloma. Results Six daratumumab trials were identified, covering 5106 subjects. Daratumumab containing combinations for untreated myeloma attained an impressive complete response or better (>= CR) rate of 24%, very good partial response or better (>= VGPR) rate of 67%, overall response rate (ORR) of 92%. Daratumumab added to standard of care significantly improved progression free survival (PFS): the HR for PFS was 0.52 [0.44, 0.61], P < .001. The HR for overall survival (OS) was 0.73 [0.52, 1.04], P = .09. In the network meta-analysis for patients ineligible for autologous stem-cell transplantation (ASCT), DRd regimen produced significant PFS advantage vs other first-line treatments (VMP HR:0.39 P < .001, Rd HR:0.55 P < .001, MPT HR:0.38 P < .001, and MP HR:0.22 P < .001); DVMP regimen also produced significant PFS advantage vs VMP (HR:0.50 P < .001), MPT (HR:0.49 P < .001), and MP (HR:0.28 P < .001). Among these first-line regimens (DRd, DVMP, VMP, Rd, MPT, and MP), DRd regimen had the highest probability to be the best intervention, with 83.4% and 91.0% probability to reach the longest PFS and OS, respectively. Toxicity consisted primarily of myelosuppression. And, the vital non-hematologic adverse events (AEs) were peripheral sensory neuropathy (41% of all grades) and upper respiratory tract infection (39% of all grades). Conclusions Daratumumab added to standard of care could produce clinical benefits in newly diagnosed patients with multiple myeloma. DRd and DVMP could be good combination options for those patients ineligible for ASCT.