Background: Treatment for transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM) has improved with anti-CD38 monoclonal antibodies. Among them, daratumumab, combined with standard therapies, has shown promising results in clinical trials. This meta-analysis consolidates evidence on the effectiveness and safety of daratumumab-based treatments for this patient group from all available randomized controlled trials (RCTs). Methods: We systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and clinical trial registries from inception to September 2025 for phase II and III RCTs comparing daratumumab-containing regimens to non-daratumumab controls in TIE NDMM patients. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included minimal residual disease (MRD) negativity rate and adverse events (AEs). Heterogeneity was assessed using I2statistics, and subgroup analyses were performed to explore potential sources of heterogeneity. Results: Six RCTs involving 2478 patients were included. Daratumumab-based regimens significantly improved PFS (hazard ratio [HR] = 0.544, 95% confidence interval [CI]: 0.483–0.612,p< 0.001; I2= 28.6%) and OS (HR = 0.693, 95% CI: 0.606–0.791,p< 0.001; I2= 30.6%). The MRD negativity rate was significantly higher with daratumumab (risk ratio [RR] = 2.322, 95% CI: 1.486–3.627,p< 0.001). Furthermore, daratumumab-based regimens yielded a four-fold increase in the rate of sustained MRD negativity (≥12 months) (RR = 3.999, 95% CI: 1.094–8.403,p< 0.001). However, these regimens were associated with increased risks of serious adverse events (SAEs) (RR = 1.146, 95% CI: 1.064–1.233,p< 0.001), overall grade 3/4 AEs (RR = 1.075, 95% CI: 1.038–1.115,p< 0.001), neutropenia, lymphopenia, infections, pneumonia, and fatal AEs. No significant differences were observed in thrombocytopenia or anemia. Conclusions: Daratumumab-based regimens significantly improve survival outcomes and the depth/durability of treatment response in TIE NDMM patients, supporting their use as first-line therapy. However, the increased risk of specific AEs necessitates careful patient selection, proactive infection prevention, and vigilant monitoring. These findings provide robust evidence for clinical practice guidelines and underscore the need to balance efficacy with safety in this vulnerable population.
背景：抗CD38单克隆抗体的应用改善了不适合移植（TIE）的新诊断多发性骨髓瘤（NDMM）的治疗。其中，达雷妥尤单抗联合标准疗法在临床试验中显示出良好前景。本荟萃分析整合了所有可获得的随机对照试验（RCT）中关于基于达雷妥尤单抗的方案对此类患者有效性和安全性的证据。方法：我们系统检索了PubMed、Embase、Cochrane对照试验中心注册库及临床试验注册平台自建库至2025年9月的文献，纳入在TIE NDMM患者中比较含达雷妥尤单抗方案与非达雷妥尤单抗对照方案的II/III期RCT。主要结局指标为无进展生存期（PFS）和总生存期（OS）。次要结局指标包括微小残留病（MRD）阴性率和不良事件（AEs）。采用I²统计量评估异质性，并进行亚组分析以探索异质性来源。结果：共纳入6项RCT，涉及2478例患者。基于达雷妥尤单抗的方案显著改善了PFS（风险比[HR] = 0.544，95%置信区间[CI]：0.483–0.612，p < 0.001；I² = 28.6%）和OS（HR = 0.693，95% CI：0.606–0.791，p < 0.001；I² = 30.6%）。达雷妥尤单抗组的MRD阴性率显著更高（风险比[RR] = 2.322，95% CI：1.486–3.627，p < 0.001）。此外，基于达雷妥尤单抗的方案使持续MRD阴性（≥12个月）率提高了四倍（RR = 3.999，95% CI：1.094–8.403，p < 0.001）。然而，这些方案与严重不良事件（SAEs）（RR = 1.146，95% CI：1.064–1.233，p < 0.001）、总体3/4级AEs（RR = 1.075，95% CI：1.038–1.115，p < 0.001）、中性粒细胞减少、淋巴细胞减少、感染、肺炎及致死性AEs的风险增加相关。在血小板减少或贫血方面未观察到显著差异。结论：基于达雷妥尤单抗的方案显著改善了TIE NDMM患者的生存结局及治疗反应的深度与持久性，支持其作为一线治疗方案。然而，特定AEs风险的增加要求进行谨慎的患者选择、积极的感染预防和严密监测。这些发现为临床实践指南提供了有力证据，并强调在此脆弱人群中需平衡疗效与安全性。
肿瘤(癌症)患者之家