Background:Recently, the addition of anti-CD38 monoclonal antibodies (mAbs) to standard first-line triplet regimens, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD) and dexamethasone, has led to the introduction of quadruplets in clinical practice.Methods:A systematic search was conducted (end-of-search: 9 November, 2024) for clinical trials investigating first-line anti-CD38 mAb-based quadruplets in combination with a PI and an IMiD. Pooled proportions and effect-estimates along with 95% confidence intervals were calculated with common-effect and random-effects models and further subgroup and meta-regression analyses were performed.Results:The pooled 2-, 3- and 4-year progression-free survival (PFS) rates were 89%, 77% and 86%, respectively. Furthermore, patients treated with quadruplets demonstrated a 46% reduced risk for disease progression or death (HR = 0.54, 95% CI: 0.46–0.64) compared to those on triplets. Overall survival (OS) rates were consistently high, ranging from 83% to 96% between different regimens. High rates of deep responses that deepened over time were observed, with the pooled proportion of patients achieving at least complete response being 64%. Importantly, the pooled MRD negativity rate was 62%, whereas patients treated with quadruplet first-line therapy had 2.5 times the odds to be MRD negative at any point compared with those on triplets. Moreover, the odds for sustained 12-month MRD negativity were thrice as much with quadruplets compared to triplets. Finally, while no increase in serious adverse events was observed with quadruplet regimens compared to triplets, a 46% statistically significant increased risk for grade 3–4 neutropenia and thrombocytopenia was observed, along with a 14% increased risk for grade 3–4 infections.Conclusions:The addition of anti-CD38 mAbs to standard triplet regimens has shown particularly favorable outcomes, supporting their integration in the upfront treatment of patients with NDMM. However, close monitoring for hematological toxicity and infections is essential.
背景：近年来，在包含蛋白酶体抑制剂（PI）、免疫调节药物（IMiD）和地塞米松的标准一线三联方案基础上加入抗CD38单克隆抗体（mAbs），推动了四联方案在临床实践中的应用。 方法：系统检索了截至2024年11月9日的临床试验，这些试验研究了基于抗CD38单克隆抗体的一线四联方案（联合PI和IMiD）。采用固定效应和随机效应模型计算汇总比例及效应估计值（含95%置信区间），并进行了亚组分析和荟萃回归分析。 结果：汇总的2年、3年和4年无进展生存（PFS）率分别为89%、77%和86%。此外，与接受三联方案治疗的患者相比，接受四联方案治疗的患者疾病进展或死亡风险降低了46%（HR = 0.54，95% CI：0.46–0.64）。不同方案的总生存（OS）率始终保持在较高水平，范围在83%至96%之间。观察到深度缓解率较高且随时间推移进一步加深，实现至少完全缓解的患者汇总比例为64%。重要的是，汇总的微小残留病（MRD）阴性率为62%，且与三联方案相比，接受一线四联方案治疗的患者在任何时间点达到MRD阴性的几率是其2.5倍。此外，与三联方案相比，四联方案实现持续12个月MRD阴性的几率是其三倍。最后，虽然四联方案与三联方案相比未观察到严重不良事件增加，但观察到3-4级中性粒细胞减少和血小板减少的风险显著增加46%，同时3-4级感染风险增加14%。 结论：在标准三联方案基础上加入抗CD38单克隆抗体显示出特别良好的疗效，支持将其整合到新诊断多发性骨髓瘤（NDMM）患者的前线治疗中。然而，必须密切监测血液学毒性和感染风险。
肿瘤(癌症)患者之家