The activity and safety of novel proteasome inhibitors strategies (single, doublet and triplet) for relapsed/refractory multiple myeloma

<b>Purpose:</b> We sought to evaluate the activity and safety of these novel proteasome inhibitors (PIs) (carfilzomib, ixazomib, oprozomib and marizomib) containing regimens (single, doublet and triplet) for relapsed/refractory multiple myeloma (R/RMM). <b>Methods:</b> We searched published reports including these novel PIs containing regimens for R/RMM. <b>Results:</b> Finally, we identified 28 prospective studies that evaluated 4123 patients. Pooled analysis showed that novel PIs doublet combinations attained an impressive overall response rate (ORR) of 67%, which was higher than that of 22% from novel PIs single-agent (<i>p</i> p = .54). And, there were no difference between them in ≥VGPR and CBR analysis. Compared to standard therapy, novel PIs combinations clearly benefited patients with R/RMM in terms of overall survival (HR, 0.79; <i>p</i>= .01), progression free survival(HR, 0.64; <i>p</i> = .01), overall response rate (RR = 1.21 <i>p</i> <b>Conclusions:</b> Novel PIs doublet combinations attained superior response outcomes over novel PIs single-agent in patients with R/RMM. Meanwhile, novel PIs triplet combinations had similar response outcomes with novel PIs doublet combinations. Compared to standard therapy, novel PIs combinations clearly prolonged survival for patients with R/RMM.