Lenalidomide, ixazomib, or daratumumab maintenance therapy in multiple myeloma

Lenalidomide, ixazomib, and daratumumab have been proposed as maintenance therapies for patients with newly diagnosed multiple myeloma (MM; NDMM). There are, however, no randomized controlled trials (RCTs) comparing them. We conducted a network meta-analysis (NMA) of RCTs comparing these agents against placebo in NDMM. A Bayesian NMA model was used to assess the relative effects of competing treatments on progression-free survival (PFS) and overall survival (OS) in 9 studies including 4115 patients with transplant-eligible MM (TEMM) and 1689 patients with non-transplant-eligible MM (NTEMM). Lenalidomide and daratumumab but not ixazomib were associated with improved PFS compared with placebo in patients with TEMM (lenalidomide [hazard ratio (HR), 0.46; 95% credible interval (CrI), 0.36-0.56]; daratumumab [HR, 0.49; 95% Crl, 0.32-0.76]; and ixazomib [HR, 0.72; 95% CrI, 0.46-1.12]) and those with NTEMM (lenalidomide [HR, 0.46; 95% CrI, 0.29-0.75] and ixazomib [HR, 0.69; 95% CrI, 0.43-1.18]). The PFS benefit for daratumumab was present regardless of whether daratumumab-based induction therapy was received. None of the agents showed an OS benefit, and PFS benefits were not seen in patients with high-risk cytogenetics. Lenalidomide was associated with second malignancies, ixazomib with thrombocytopenia, and daratumumab with pneumonia. We propose that lenalidomide remains the maintenance therapy of choice for NDMM.