Nizamuddin Imran A, Bartlett Nancy L
Department of Medicine, Division of Oncology, Washington University School of Medicine in St. Louis.
Haematologica. 2025 Jul 1;110(7):1472-1482. doi: 10.3324/haematol.2024.285245. Epub 2024 Oct 31.
Bispecific antibodies, specifically anti-CD20 T-cell engaging constructs, are poised to alter the treatment paradigm for multiple B-cell malignancies, including follicular lymphoma. Two CD20xCD3 bispecific antibodies, mosunetuzumab and epcoritamab, are now approved in the United States for third-line or later treatment of follicular lymphoma. A third agent, odronextamab, remains under review by regulatory agencies. In pivotal phase II trials, these bispecific antibodies demonstrated overall response rates of approximately 80%, with complete response rates of 60-70%, the majority of which have been durable at 2 years. Important safety signals included risk of infections, neutropenia, and cytokine release syndrome, which occurred in approximately half of patients, but was rarely high grade. Despite similar efficacy and toxicity profiles, key differences exist among agents, primarily relating to treatment duration, route of administration, and prophylactic corticosteroid use. Several ongoing studies are exploring bispecific antibodies in earlier lines of treatment, either as single agents or in combination with other active therapies. This novel class of agents is likely to play a pivotal role in improving outcomes for patients with follicular lymphoma.
双特异性抗体，特别是抗CD20 T细胞衔接构建体，有望改变包括滤泡性淋巴瘤在内的多种B细胞恶性肿瘤的治疗模式。两种CD20xCD3双特异性抗体，即莫苏奈妥珠单抗和依泊妥单抗，现已在美国获批用于滤泡性淋巴瘤的三线或后续治疗。第三种药物奥多奈妥单抗仍在接受监管机构的审查。在关键的II期试验中，这些双特异性抗体的总缓解率约为80%，完全缓解率为60-70%，其中大多数在2年时仍持续有效。重要的安全信号包括感染风险、中性粒细胞减少和细胞因子释放综合征，约一半的患者出现这些情况，但很少是高级别。尽管疗效和毒性特征相似，但各药物之间存在关键差异，主要涉及治疗持续时间、给药途径和预防性使用皮质类固醇。几项正在进行的研究正在探索双特异性抗体在早期治疗中的应用，要么作为单一药物，要么与其他有效疗法联合使用。这类新型药物可能在改善滤泡性淋巴瘤患者的预后方面发挥关键作用。
