The use of 4-drug induction regimens for treatment naïve newly diagnosed multiple myeloma (NDMM) is associated with improved depth of response and progression-free survival (PFS). However, head-to-head trials of 4-drug combinations are lacking, and instead, these regimens are typically compared to 3-drug backbones; limiting the ability to discern whether any additional benefit (or toxicity) is simply additive or represents a synergy (or interaction). We conducted a meta-analysis of phase 2 and phase 3 clinical trials that randomized treatment naïve NDMM patients to either a 4-drug or 3-drug induction regimen. We included 11 trials which represented 6509 unique patients. PFS for all trials in the meta-analysis was 54 months with a 4-drug induction and 8.9 months with a 3-drug induction (HR: 0.49; 95% CI: 0.45; 0.54), but there was no benefit to using a 4-drug induction that did not include an anti-CD38 antibody (PFS 4-drug 8.1 months, PFS 3-drug 8.0 months; HR 0.95; 95% CI 0.86; 1.06). Adverse events were more frequent with the quadruplet regimens but were predominately mild. High-grade (≥3) adverse events (AEs) that were more common with 4-drug regimens were infections (RR: 1.34; 95% CI 1.17; 1.54) and thrombocytopenia (RR: 1.39; 95% CI 1.12; 1.74). This study suggests that 4-drug induction regimens which include an anti-CD38 antibody improve efficacy although with additional toxicity in NDMM patients.
对于初治新诊断多发性骨髓瘤（NDMM）患者，采用四药诱导治疗方案与提高治疗反应深度及延长无进展生存期（PFS）相关。然而，目前缺乏四药联合方案的头对头临床试验，这些方案通常仅与三药基础方案进行比较，从而难以明确其额外获益（或毒性）究竟是简单的累加效应，还是存在协同作用（或交互效应）。我们对将初治NDMM患者随机分配至四药或三药诱导治疗方案的II期和III期临床试验进行了荟萃分析，共纳入11项试验，涉及6509例独立患者。荟萃分析中所有试验的汇总数据显示，四药诱导治疗的PFS为54个月，而三药诱导治疗为8.9个月（风险比[HR]：0.49；95%置信区间[CI]：0.45-0.54），但未包含抗CD38抗体的四药方案并未显示获益（四药PFS 8.1个月，三药PFS 8.0个月；HR 0.95；95% CI 0.86-1.06）。四药方案的不良事件发生率更高，但以轻度为主。在四药方案中更常见的高级别（≥3级）不良事件包括感染（相对风险[RR]：1.34；95% CI 1.17-1.54）和血小板减少症（RR：1.39；95% CI 1.12-1.74）。本研究表明，包含抗CD38抗体的四药诱导方案可提高NDMM患者的疗效，但同时也增加了毒性风险。
肿瘤(癌症)患者之家