Ntanasis-Stathopoulos Ioannis, Filippatos Charalampos, Malandrakis Panagiotis, Koutoulidis Vassilis, Kastritis Efstathios, Terpos Evangelos, Dimopoulos Meletios-Athanasios, Gavriatopoulou Maria
Department of Clinical Therapeutics, Alexandra General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.
First Department of Radiology, Areteion Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.
Cancers (Basel). 2025 Jun 11;17(12):1943. doi: 10.3390/cancers17121943.
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. 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. 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. 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.
最近，在包括蛋白酶体抑制剂（PI）、免疫调节药物（IMiD）和地塞米松的标准一线三联方案中加入抗CD38单克隆抗体（mAb），已促使四联方案在临床实践中得以应用。我们进行了一项系统检索（检索截止日期：2024年11月9日），以查找研究基于抗CD38 mAb的一线四联方案联合PI和IMiD的临床试验。采用固定效应模型和随机效应模型计算合并比例和效应估计值以及95%置信区间，并进一步进行亚组分析和meta回归分析。2年、3年和4年的无进展生存期（PFS）合并率分别为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）。总生存期（OS）率一直很高，不同方案之间的OS率在83%至96%之间。观察到深度缓解率随着时间推移不断提高，达到至少完全缓解的患者合并比例为64%。重要的是，合并的微小残留病（MRD）阴性率为62%，而接受一线四联疗法治疗的患者在任何时间点MRD阴性的几率是接受三联方案治疗患者的2.5倍。此外，四联方案组患者持续12个月MRD阴性的几率是三联方案组的三倍。最后，虽然与三联方案相比，四联方案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有46%的统计学显著增加，3 - 4级感染风险增加了14%。在标准三联方案中加入抗CD38 mAb已显示出特别良好的效果，支持将其纳入新诊断的多发性骨髓瘤（NDMM）患者的一线治疗。然而，密切监测血液学毒性和感染至关重要。
