■本研究旨在通过荟萃分析评估复发性/难治性多发性骨髓瘤(RRMM)患者中抗CD38单克隆抗体(mAb)的安全性和有效性。
■截至2023年6月,我们搜索了PubMed,WebofScience,Embase和Cochrane图书馆。包括随机对照试验(RCT),该试验比较了抗CD38mAb加免疫调节药物(IMiDs)或蛋白酶体抑制剂(PIs)加地塞米松和IMiDs(或PIs)以及地塞米松单独治疗RRMM患者的临床结果。主要通过无进展生存期(PFS)和总生存期(OS)评估疗效。用血液学和非血液学治疗引起的不良事件(TEAE)分析安全性。所有结果都使用风险比(HR)进行汇总,相对风险(RR),及其95%置信区间(CI)和预测区间(PI)。
■这项荟萃分析总共包括11项随机对照试验。与单独使用IMiDs(或PI)和地塞米松相比,抗CD38mAb联合IMiDs(或PIs)和地塞米松显著延长RRMM患者的PFS(HR:0.552,95%CI=0.461~0.659,95%PI=0.318~0.957)和OS(HR:0.737,95%CI=0.657~0.827,95%PI=0.626~0.868).此外,接受抗CD38mAb联合IMiD(或PI)和地塞米松的RRMM患者获得了更高的总体反应率(RR:1.281,95%CI=1.144至1.434,95%PI=0.883至1.859),完全反应或更好(RR:2.602,95%CI=1.977至3.424,95%PI=1.203至5.628),非常好的部分反应(VGPR)或更好(RR:1.886,95%CI=1.532至2.322,95%PI=0.953至3.731),与仅接受IMiDs(或PIs)和地塞米松的患者相比,最小残留病(MRD)阴性(RR:4.147,95%CI=2.588至6.644,95%PI=1.056至16.283)。对于TEAE,血液学和非血液学TEAE的发生率,包括血小板减少症,中性粒细胞减少症,上呼吸道感染(URTI),肺炎,支气管炎,呼吸困难,腹泻,发热,背痛,关节痛,疲劳,失眠,和高血压,与IMiDs(或PIs)和地塞米松组组合的抗CD38mAb高于IMiDs(或PIs)和地塞米松组。
■我们的研究表明,抗CD38mAb与IMiDs(或PIs)和地塞米松联合使用可改善PFS和OS,并实现了更高的总体反应率,完全反应或更好,VGPR或更好,MRD阴性,以及更高的血小板减少率,中性粒细胞减少症,URTI,肺炎,支气管炎,呼吸困难,腹泻,发热,背痛,关节痛,疲劳,失眠,RRMM患者的高血压。
■https://www.crd.约克。AC.英国/PROSPERO/,标识符CRD42023431071。
UNASSIGNED: The current study aims to evaluate the safety and efficacy of anti-CD38 monoclonal antibodies (mAbs) among patients with relapsed/refractory multiple myeloma (RRMM) through meta-analysis.
UNASSIGNED: As of June 2023, we searched PubMed, Web of Science, Embase and the Cochrane Library. Randomized controlled trials (RCTs) which compared the clinical outcomes of anti-CD38 mAbs plus immunomodulatory drugs (IMiDs) or proteasome inhibitors (PIs) plus dexamethasone and IMiDs (or PIs) and dexamethasone alone for RRMM patients were included. Efficacy outcomes were mainly evaluated with progression-free survival (PFS) and overall survival (OS). The safety was analyzed with hematologic and nonhematologic treatment-emergent adverse events (TEAEs). All results were pooled using hazard ratio (HR), relative risk (RR), and their 95% confidence interval (CI) and prediction interval (PI).
UNASSIGNED: This meta-analysis included 11 RCTs in total. Compared with IMiDs (or PIs) and dexamethasone alone, anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone significantly prolonged PFS (HR: 0.552, 95% CI = 0.461 to 0.659, 95% PI = 0.318 to 0.957) and OS (HR: 0.737, 95% CI = 0.657 to 0.827, 95% PI = 0.626 to 0.868) in patients with RRMM. Additionally, RRMM patients receiving anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone achieved higher rates of overall response (RR: 1.281, 95% CI = 1.144 to 1.434, 95% PI = 0.883 to 1.859), complete response or better (RR: 2.602, 95% CI = 1.977 to 3.424, 95% PI = 1.203 to 5.628), very good partial response (VGPR) or better (RR: 1.886, 95% CI = 1.532 to 2.322, 95% PI = 0.953 to 3.731), and minimum residual disease (MRD)-negative (RR: 4.147, 95% CI = 2.588 to 6.644, 95% PI = 1.056 to 16.283) than those receiving IMiDs (or PIs) and dexamethasone alone. For TEAEs, the rates of hematologic and nonhematologic TEAEs, including thrombocytopenia, neutropenia, upper respiratory tract infection (URTI), pneumonia, bronchitis, dyspnea, diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension, were higher in the anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone group than in the IMiDs (or PIs) and dexamethasone group.
UNASSIGNED: Our study showed that anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone improved PFS and OS, and achieved higher rates of overall response, complete response or better, VGPR or better, and MRD-negative, as well as higher rates of thrombocytopenia, neutropenia, URTI, pneumonia, bronchitis, dyspnea, diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension in RRMM patients.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023431071.