Shouse Geoffrey
City of Hope National Medical Center, Duarte, CA, United States of America.
Blood Rev. 2025 Jan;69:101251. doi: 10.1016/j.blre.2024.101251. Epub 2024 Nov 26.
Bispecific antibody therapy has revolutionized the treatment of hematologic malignancies. There are currently 7 FDA approved products with 4 different targets covering 5 indications in 4 diseases. Products include blinatumomab targeting B-cell ALL in MRD detectable first remission and in relapsed and/or refractory disease, elranatamab and teclistamab targeting BCMA in relapsed/refractory multiple myeloma, talquetamab targeting GPCR5D in multiple myeloma, and mosunetuzumab, epcoritamab and glofitamab which all target CD20 in follicular lymphoma, both follicular and large B cell lymphoma, or large B cell lymphoma alone, respectively. Each product utilizes the strategy of T-cell redirection by binding CD3 on the effector cell to target immune cells toward a tumor associated antigen. There are overlapping toxicities related to activation of the immune system and inflammation. The role of these agents in earlier lines of therapy and in novel combinations are under heavy investigation and their full utility and benefit in the treatment of hematologic malignancies is yet to be fully realized.
双特异性抗体疗法彻底改变了血液系统恶性肿瘤的治疗方式。目前有7种获得美国食品药品监督管理局（FDA）批准的产品，其具有4种不同靶点，涵盖4种疾病的5种适应症。这些产品包括在微小残留病（MRD）可检测的首次缓解期以及复发和/或难治性疾病中靶向B细胞急性淋巴细胞白血病（ALL）的贝林妥欧单抗；在复发/难治性多发性骨髓瘤中靶向B细胞成熟抗原（BCMA）的埃拉纳妥单抗和替西他单抗；在多发性骨髓瘤中靶向G蛋白偶联受体5D（GPCR5D）的塔奎他单抗；以及分别在滤泡性淋巴瘤、滤泡性和大B细胞淋巴瘤或仅大B细胞淋巴瘤中均靶向CD20的莫苏奈妥单抗、依泊妥单抗和格洛菲妥单抗。每种产品都采用了通过结合效应细胞上的CD3将免疫细胞重定向至肿瘤相关抗原的策略。存在与免疫系统激活和炎症相关的重叠毒性。这些药物在早期治疗线和新型联合治疗中的作用正在深入研究中，它们在血液系统恶性肿瘤治疗中的全部效用和益处尚未完全实现。
