Evaluation of anti-CD38 monoclonal antibody-based immunotherapy in multiple myeloma with renal insufficiency: a systematic review and meta-analysis.

Abstract

Background: Renal impairment is one of the common characteristics of multiple myeloma (MM) and makes management of MM more complicated. Even though monoclonal antibodies targeting CD38 have wildly succeeded in treating MM, the addition of anti-CD38 monoclonal antibodies to standard therapy to treat MM patients with renal insufficiency is still poorly studied.

Objectives: This study aims to evaluate whether using anti-CD38 monoclonal antibody-based immunotherapy would improve the prognosis of MM patients with renal insufficiency.

Design: This is a systematic review and meta-analysis.

Data sources and methods: We searched Scopus, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase, and Web of Science Core Collection for randomized controlled trials that enrolled patients with MM who received CD38-targeting monoclonal antibody regimens and reported the efficacy and survival of MM with renal insufficiency. We then performed a meta-analysis to estimate the efficacy of adding anti-CD38 monoclonal antibodies to backbone regimens in MM with renal insufficiency.

Results: In 7594 studies screened, 12 phase III trials were eligible, including 5 trials for newly diagnosed MM (NDMM; 3194 patients; 1261 with renal insufficiency) and 7 trials for relapsed refractory MM (RRMM; 2657 patients; 648 with renal insufficiency). Among NDMM patients with renal insufficiency, the addition of anti-CD38 monoclonal antibody to backbone regimens was associated with improved progression-free survival (PFS; pooled HR, 0.50; 95% CI, 0.38-0.67; p < 0.001), with little evidence of heterogeneity (Cochran Q, p = 0.19; I ² = 34.7%). Similar results were seen among RRMM patients with renal insufficiency (pooled HR, 0.46; 95% CI, 0.37-0.57; p < 0.001), with no evidence of heterogeneity (Cochran Q, p = 0.89; I ² = 0%). Similarly, the addition of anti-CD38 monoclonal antibody in RRMM among patients with renal insufficiency was associated with improved overall survival (OS; pooled HR, 0.70; 95% CI, 0.57-0.88; p = 0.002), with no significant heterogeneity (Cochran Q, p = 0.69; I ² = 0%).

Conclusion: This meta-analysis suggests that the addition of anti-CD38 monoclonal antibodies benefits PFS in both NDMM and RRMM with renal insufficiency and OS in RRMM patients with renal insufficiency.