Many clinical trials have assessed the effect and safety of monoclonal antibodies (MAbs) in combination with proteasome inhibitors or immunomodulators plus dexamethasone/prednisone for the treatment of multiple myeloma (MM). The treatment outcomes of comparing different MAbs in combination with the above-mentioned agents remained unclear. We performed the meta-analysis to indirectly compare the effect and safety of MAbs targeting CD38, SLAMF7, and PD-1/PD-L1 in combination with bortezomib/immunomodulators plus dexamethasone/prednisone for patients with MM. We searched thoroughly in the databases for randomised controlled trials (RCTs) in which at least one of the three MAbs were included. We included eleven eligible RCTs with 5367 patients in the meta-analysis. Statistical analysis was carried out using StataMP14 and Indirect Treatment Comparisons software. We calculated hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and relative risk (RR) for overall response rate, complete response (CR) or better, very good partial response (VGPR) or better, VGPR, partial response, stable disease, and grade 3 or higher adverse events among the three groups. The HRs for PFS of the CD38 group vs SLAMF7 group, CD38 group vs PD-1/PD-L1 group, and SLAMF7 group vs PD-1/PD-L1 group were 0.662 (95%CI 0.543–0.806), 0.317 (95%CI 0.221–0.454), and 0.479 (95%CI 0.328–0.699), respectively. The HR for OS of the CD38 group vs SLAMF7 group was 0.812 (95%CI 0.584–1.127). The RR for CR or better in the CD38 group vs SLAMF7 group was 2.253 (95%CI 1.284–3.955). The RR for neutropenia of the CD38 group vs SLAMF7 group was 1.818 (95%CI 1.41–2.344). Treatment with the CD38 group had longer PFS and better treatment response than that with the SLAMF7 or PD-1/PD-L1 group. In addition, the SLAMF7 group prolonged PFS compared with the PD-1/PD-L1 group and was associated with a lower incidence of grade 3 or higher neutropenia than the CD38 and PD-1/PD-L1 group. In conclusion, MAbs targeting CD38 are the best, followed by those targeting SLAMF7; MAbs targeting PD-1/PD-L1 are the worst when in combination with bortezomib/immunomodulators plus dexamethasone/prednisone for the treatment of MM.

中文翻译：

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靶向 CD38、SLAMF7 和 PD-1/PD-L1 的单克隆抗体联合硼替佐米/免疫调节剂加地塞米松/强的松治疗多发性骨髓瘤的比较：随机对照试验的间接比较 Meta 分析

许多临床试验评估了单克隆抗体 (MAb) 与蛋白酶体抑制剂或免疫调节剂联合地塞米松/泼尼松治疗多发性骨髓瘤 (MM) 的效果和安全性。比较不同 MAb 与上述药物组合的治疗结果仍不清楚。我们进行了荟萃分析，以间接比较靶向 CD38、SLAMF7 和 PD-1/PD-L1 的单克隆抗体联合硼替佐米/免疫调节剂加地塞米松/泼尼松治疗 MM 患者的效果和安全性。我们在数据库中彻底搜索了随机对照试验 (RCT)，其中至少包括了三种 MAb 中的一种。我们在荟萃分析中纳入了 11 项符合条件的随机对照试验，共 5367 名患者。使用StataMP14和间接治疗比较软件进行统计分析。我们计算了总生存期 (OS) 和无进展生存期 (PFS) 的风险比 (HRs) 以及总反应率、完全反应 (CR) 或更好、非常好的部分反应 (VGPR) 或更好的相对风险 (RR)，三组中的 VGPR、部分缓解、疾病稳定和 3 级或更高的不良事件。CD38 组 vs SLAMF7 组、CD38 组 vs PD-1/PD-L1 组、SLAMF7 组 vs PD-1/PD-L1 组 PFS 的 HR 分别为 0.662（95%CI 0.543–0.806）、0.317（95 %CI 0.221–0.454) 和 0.479 (95%CI 0.328–0.699)。CD38 组与 SLAMF7 组的 OS 的 HR 为 0.812 (95%CI 0.584–1.127)。CD38 组与 SLAMF7 组的 CR 或更好的 RR 为 2.253 (95%CI 1.284–3.955)。CD38 组与 SLAMF7 组的中性粒细胞减少症的 RR 为 1.818 (95%CI 1.41–2.344)。与 SLAMF7 或 PD-1/PD-L1 组相比，CD38 组治疗具有更长的 PFS 和更好的治疗反应。此外，与 PD-1/PD-L1 组相比，SLAMF7 组延长了 PFS，并且与 CD38 和 PD-1/PD-L1 组相比，3 级或更高的中性粒细胞减少发生率更低。总之，靶向 CD38 的 MAb 是最好的，其次是靶向 SLAMF7 的；与硼替佐米/免疫调节剂加地塞米松/强的松联合治疗 MM 时，靶向 PD-1/PD-L1 的单克隆抗体最差。与 PD-1/PD-L1 组相比，SLAMF7 组延长了 PFS，并且与 CD38 和 PD-1/PD-L1 组相比，3 级或更高的中性粒细胞减少发生率更低。总之，靶向 CD38 的 MAb 是最好的，其次是靶向 SLAMF7 的；与硼替佐米/免疫调节剂加地塞米松/强的松联合治疗 MM 时，靶向 PD-1/PD-L1 的单克隆抗体最差。与 PD-1/PD-L1 组相比，SLAMF7 组延长了 PFS，并且与 CD38 和 PD-1/PD-L1 组相比，3 级或更高的中性粒细胞减少发生率更低。总之，靶向 CD38 的 MAb 是最好的，其次是靶向 SLAMF7 的；与硼替佐米/免疫调节剂加地塞米松/强的松联合治疗 MM 时，靶向 PD-1/PD-L1 的单克隆抗体最差。