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

Purpose: 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). Methods: We searched published reports including these novel PIs containing regimens for R/RMM. Results: 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 (p 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; p= .01), progression free survival(HR, 0.64; p = .01), overall response rate (RR = 1.21 p Conclusions: 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.研究目的：本研究旨在评估含新型蛋白酶体抑制剂（proteasome inhibitors, PIs）（卡非佐米、伊沙佐米、奥佐米德与马立佐米）的单药、双药及三药治疗方案，用于复发难治性多发性骨髓瘤（relapsed/refractory multiple myeloma, R/RMM）的疗效与安全性。 研究方法：本研究检索了已发表的、针对复发难治性多发性骨髓瘤的新型蛋白酶体抑制剂联合治疗方案相关报道。 研究结果：最终共纳入28项前瞻性研究，共计4123例受试患者。合并分析结果显示，新型蛋白酶体抑制剂双药联合方案的总体缓解率（overall response rate, ORR）高达67%，高于新型蛋白酶体抑制剂单药方案的22%（P=0.54）；且≥非常好的部分缓解（very good partial response, VGPR）率与临床获益率（clinical benefit rate, CBR）分析均未显示组间存在显著差异。与标准治疗方案相比，新型蛋白酶体抑制剂联合方案可显著改善复发难治性多发性骨髓瘤患者的总生存期（风险比HR=0.79；P=0.01）与无进展生存期（风险比HR=0.64；P=0.01），总体缓解率相对风险RR=1.21，P=。 研究结论：针对复发难治性多发性骨髓瘤患者，新型蛋白酶体抑制剂双药联合方案的缓解效果优于单药方案。与此同时，新型蛋白酶体抑制剂三药联合方案的缓解效果与双药联合方案相当。与标准治疗方案相比，新型蛋白酶体抑制剂联合方案可显著延长复发难治性多发性骨髓瘤患者的生存时长。