Background: Despite recent advances in the treatment of multiple myeloma (MM), the disease remains incurable. Agents targeting the programmed death-1 (PD-1) axis have become key treatments for many cancers; however, monotherapies with PD-1/PD-L-1 inhibitors (PD-1i) have shown a limited efficacy in MM patients. We conducted a meta-analysis to evaluate the safety and efficacy of PD-1i in combination with standard of care (SOC) therapies for MM. Methods: A systematic search identified phase II and III randomized clinical trials involving MM patients treated with PD-1i, using terms such as “Relapsed Multiple Myeloma” and “PD-1 inhibitors.” The search included trials published in English after 2016 using the PubMed, CINAHL, and Cochrane databases. Data were analyzed using RStudio v4.4.2, with survival data assessed using Kaplan–Meier methods and Cox proportional hazards analysis. Results: Our search yielded 19 total trials, of which 5 (representing 889 unique patients) met the criteria for inclusion. A total of 488 patients received PD-1i + SOC, and 401 received SOC alone. The median progression-free survival (PFS) was 6.26 months for the PD-1i + SOC group and 7.34 months for the SOC alone group (HR, 1.2; 95% CI: 0.95–1.41;p= 0.14). The median overall survival (OS) was 22.49 months for PD-1i + SOC compared to 24.38 months for SOC alone (HR, 1.11; 95% CI: 0.87–1.42,p= 0.36). The PD-1i group showed a higher incidence of all-grade pneumonia (RR = 1.44, 95% CI: 1.03–2.02,p= 0.03), grade ≥ 3 neutropenia (RR = 1.36, 95% CI: 1.00–1.85,p= 0.05), immune-mediated adverse events (RR = 10.1, 95% CI: 0.38–271.1,p= 0.17), and grade ≥ 3 irAEs (RR = 9.59, 95% CI: 0.62–148.8,p= 0.11). Conclusion: This analysis highlights the limited efficacy and increased toxicity of adding PD-1i to SOC in MM patients. Further research is needed to explore whether targeting the PD-1/PD-L1 axis in combination with novel therapies can safely enhance the therapeutic efficacy in MM patients.
背景：尽管多发性骨髓瘤（MM）的治疗近期取得了进展，该疾病仍无法治愈。靶向程序性死亡受体-1（PD-1）轴的药物已成为多种癌症的关键治疗手段；然而，PD-1/PD-L1抑制剂（PD-1i）单药治疗在MM患者中疗效有限。我们通过荟萃分析评估PD-1i联合标准治疗（SOC）方案治疗MM的安全性与有效性。方法：通过系统检索，使用“复发多发性骨髓瘤”“PD-1抑制剂”等关键词，筛选出涉及PD-1i治疗MM患者的II期和III期随机临床试验。检索范围涵盖2016年后发表于PubMed、CINAHL和Cochrane数据库的英文文献。使用RStudio v4.4.2进行数据分析，采用Kaplan-Meier法和Cox比例风险模型评估生存数据。结果：共检索到19项试验，其中5项（涉及889例独立患者）符合纳入标准。488例患者接受PD-1i+SOC治疗，401例患者仅接受SOC治疗。PD-1i+SOC组的中位无进展生存期（PFS）为6.26个月，SOC单药组为7.34个月（HR=1.2，95% CI：0.95-1.41，p=0.14）。PD-1i+SOC组的中位总生存期（OS）为22.49个月，SOC单药组为24.38个月（HR=1.11，95% CI：0.87-1.42，p=0.36）。PD-1i组全级别肺炎（RR=1.44，95% CI：1.03-2.02，p=0.03）、≥3级中性粒细胞减少症（RR=1.36，95% CI：1.00-1.85，p=0.05）、免疫介导不良事件（RR=10.1，95% CI：0.38-271.1，p=0.17）及≥3级免疫相关不良事件（RR=9.59，95% CI：0.62-148.8，p=0.11）的发生率均更高。结论：本分析表明，在MM患者的SOC方案中联合PD-1i疗效有限且增加毒性风险。未来需进一步研究PD-1/PD-L1轴靶向治疗联合新型疗法能否安全提升MM患者的治疗效果。
肿瘤(癌症)患者之家