Lenalidomide, Ixazomib or Daratumumab Maintenance Therapy in Multiple Myeloma

Lenalidomide remains the maintenance therapy of choice for patients with newly diagnosed multiple myeloma

Lenalidomide, ixazomib and daratumumab have been proposed as maintenance therapies for patients with newly diagnosed multiple myeloma (NDMM). There are however no randomised 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 nine studies including 4115 transplant eligible (TEMM) and 1689 non-transplant eligible (NTEMM) patients. Lenalidomide and daratumumab but not ixazomib were associated with improved PFS compared to placebo in TEMM (Lenalidomide: Hazard Ratio (HR) 0.46, 95% Credible Interval (CrI) 0.36 to 0.56; Daratumumab: HR 0.49, 95% Crl 0.32 to 0.76, Ixazomib: HR 0.72, 95% CrI 0.46 to 1.12) and NTEMM patients (Lenalidomide: HR 0.46, 95% CrI 0.29 to 0.75; Ixazomib: HR 0.69, 95% CrI 0.43 to 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.