Comparative efficacy of novel-drugs combined therapeutic regimens on relapsed/refractory multiple myeloma: a network meta-analysis.

BACKGROUND: Although multiple myeloma is still incurable, an abundance of novel treatments have become available for relapsed and or refractory multiple myeloma (RRMM). Direct head-to-head comparisons between the novel treatments are lacking. We performed a network meta-analysis to evaluate immediate effects such as response quality of current novel-drugs combined therapeutic regimens, with the aim to identify treatments that could be more effective than others in RRMM.

METHODS: We searched Cochrane Library, PubMed, Embase, and Web of Science for randomized controlled clinical trials receiving novel-drugs combined treatments as means of interventions. The primary endpoint was objective response rates (ORRs). We used the surface under the cumulative ranking curve (SUCRA) to sequence treatments. Totally, 22 randomized controlled trials were identified for final evaluation. With the aim to include all regimens within one network analysis, we divided the treatment schemes into 13 categories according to the use of novel drugs.

RESULTS: Carfilzomib-, daratumumab-, and isatuximab-based treatments had better ORRs than bortezomib combined dexamethasone and lenalidomide combined dexamethasone. Daratumumab- and isatuximab-based treatments had better ORRs than pomalidomide combined dexamethasone. According to the SUCRA, daratumumab- and isatuximab-based triple-drug regimens had higher probabilities of achieving better ORRs, followed by carfilzomib, elotuzumab, venetoclax, selinexor, ixazomib, vorinostat, pomalidomide, panobinostat, lenalidomide.

CONCLUSIONS: Our network meta-analysis performed a complete review of the ORRs of all current available novel-drugs based regimens for RRMM. By using the clinical data all from randomized controlled studies, daratumumab- and isatuximab-based treatments were identified to be the best treatments receiving better response quality.