Bispecific antibodies (BsAbs) have shown promise in the management of relapsed/refractory multiple myeloma (MM). Despite its efficacy, this class of drugs is associated with significant toxicities. In this study, we conducted a pooled analysis of the available clinical trials on BsAbs for the treatment of MM, including full publications and abstracts until April 2025. BsAbs were classified into two groups: B-cell maturation antigen (BCMA), and GPRC5D/FcRH5 BsAbs. Welch’s t-test was performed to compare the safety profiles of each agent. For clustering, we used principal component analysis (PCA). Our study analyzed 22 trials involving 2374 patients with MM from early 2023 to April 2025. Among these, 1276 patients received BCMA BsAbs, 841 treated with GPRC5D/FcRH5 BsAbs, 157 received teclistamab + talquetamab, and 65 patients received a talquetamab + daratumumab, and 35 patients received talquetamab + pomalidomide. The median follow-up for all groups was 11.83 months. Among all-grade hematologic adverse events (AEs), neutropenia occurred in 40.4%, anemia in 39.2%, thrombocytopenia in 21.4%, lymphopenia in 19.2%, infections in 45.8%, and cytokine release syndrome (CRS) in 65%. For grade 3/4 AEs, infections occurred in 20.3%, CRS in 1.5%, neutropenia in 35.2%, anemia in 24.5%%, thrombocytopenia in 13.5%, and lymphopenia in 17.7%. CRS and the need for tocilizumab were significantly less frequent with BCMA BsAbs vs GPRC5D/FcRH5 BsAbs, (P < 0.002). Skillings Mack (Generalized Friedman’s) findings emphasized substantial distinctions between BCMA and GPRC5D/FcRH5×CD3 in both overall and severe grade 3/4 AEs (p ≤ 0.0002). PCA revealed agents with all grades and grade 3/4 showed similar clustering patterns except for three agents. Overall, our findings demonstrated the excellent efficacy on the use of BsAbs in MM; however, these agents have been linked to a unique AE profile. GPRC5D/FcRH5 are associated with less grade 3/4 hematologic toxicity whereas BCMA BsAbs were associated with lower grade 3/4 CRS rates, compared to GPRC5D/FcRH5. These insights are crucial for guiding treatment decisions and developing strategies to improve patient outcomes.
双特异性抗体（BsAbs）在治疗复发/难治性多发性骨髓瘤（MM）中显示出良好的前景。尽管疗效显著，此类药物仍伴随显著毒性。本研究对截至2025年4月已发表的关于BsAbs治疗MM的临床试验（包括全文和摘要）进行了荟萃分析。BsAbs分为两类：B细胞成熟抗原（BCMA）靶向BsAbs与GPRC5D/FcRH5靶向BsAbs。采用Welch's t检验比较各药物的安全性特征，并运用主成分分析（PCA）进行聚类分析。本研究共分析了2023年初至2025年4月期间的22项临床试验，涉及2374例MM患者。其中1276例接受了BCMA BsAbs治疗，841例接受了GPRC5D/FcRH5 BsAbs治疗，157例接受了teclistamab联合talquetamab治疗，65例接受了talquetamab联合daratumumab治疗，35例接受了talquetamab联合pomalidomide治疗。所有组的中位随访时间为11.83个月。在所有级别的血液学不良事件（AEs）中，中性粒细胞减少发生率为40.4%，贫血39.2%，血小板减少21.4%，淋巴细胞减少19.2%，感染45.8%，细胞因子释放综合征（CRS）65%。在3/4级AEs中，感染发生率为20.3%，CRS为1.5%，中性粒细胞减少35.2%，贫血24.5%，血小板减少13.5%，淋巴细胞减少17.7%。与GPRC5D/FcRH5 BsAbs相比，BCMA BsAbs的CRS发生率及托珠单抗使用需求显著更低（P < 0.002）。Skillings Mack（广义Friedman）检验结果强调，BCMA与GPRC5D/FcRH5×CD3两组在总体及严重3/4级AEs方面均存在显著差异（p ≤ 0.0002）。主成分分析显示，除三种药物外，其余药物在全级别与3/4级AEs中的聚类模式相似。总体而言，我们的研究证实了BsAbs在MM治疗中的优异疗效，但此类药物具有独特的不良事件特征。与GPRC5D/FcRH5 BsAbs相比，GPRC5D/FcRH5靶向药物与较低的3/4级血液学毒性相关，而BCMA BsAbs则与较低的3/4级CRS发生率相关。这些发现对于指导治疗决策及制定改善患者预后的策略至关重要。
肿瘤(癌症)患者之家