OBJECTIVES: Although the outcomes of multiple myeloma (MM) have improved, relapsed and refractory MM (RRMM) remains a major challenge (RRMM). Selinexor is a very recent first-in-class, oral selective-inhibitor-of-nuclear-export (SINE) compound that impedes Exportin 1. This is the first meta-analysis to determine the efficacy and safety of selinexor, including in combination, for RRMM.

METHODS: We conducted a comprehensive literature search until September 10, 2020, to identify literature related to the efficacy and safety of selinexor alone or in combination with corticosteroids and proteasome inhibitors for the treatment of RRMM. Independent reviewers performed study selection, data extraction, and the risk of bias assessment based on Cochrane criteria. The primary outcome measures of interest were efficacy outcomes, with safety outcomes being of secondary interest. Statistical analyses using a fixed/random effects model were performed, at a statistical significance of p<0.05. The RevMan software was used for analysis.

RESULTS: A total of five phases I-II clinical trials were included, including a total of 348 RRMM patients. Most of the patients were scored between 0-2 based on Eastern Cooperative Oncology Group (ECOG) performance-status scoring. Meta-analysis of all the studies found significant overall clinical benefit rate (47.5, 95% confidence interval [CI] 23.9-71.0, P<0.0001), overall response rate (35.3, 95% CI 17.1-53.6, P=0.0001), and complete response (2.6, 95% CI 0.3-4.9, P=0.03). For safety outcomes, only the rate of discontinuations was significant with selinexor (19.4, 95% CI 13.4-25.5; P<0.00001). Subgroup analyses demonstrated that the efficacy is higher with selinexor combinations compared to selinexor alone, and suggested that outcomes may vary based on the refractory status of the MM.

CONCLUSIONS: Based on the type of included studies, this is a pilot analysis that demonstrated that selinexor produces significantly better responses with an acceptable safety profile in RRMM patients. Combination with other drugs produces a better response with no additional safety concerns.