Lenalidomide, ixazomib, or daratumumab maintenance therapy in multiple myeloma

Abstract

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.

Graphical abstract

Figure 1.

PRISMA flowchart describing the selection of studies. Literature search yielded a total of 1938 results. After a 2-staged screening (as mentioned in the text), unsuitable reports were excluded, and a total of 9 studies (45 records) were included.

Figure 2.

Comparison of PFS between maintenance strategies for transplant-eligible patients. “b” indicates sensitivity analysis using data from the CASSIOPEIA trial focusing on patients who did not have Dara as induction therapy. Dara, daratumumab; Ixa, ixazomib; Len, lenalidomide.

Figure 3.

Comparison of PFS and OS between maintenance strategies for non–transplant-eligible patients. “b” indicates sensitivity analysis by excluding Zweegman et al trial.