Expert Opinion on Biological Therapy ( IF 4.6 ) Pub Date : 2020-11-09 , DOI: 10.1080/14712598.2020.1822318 Christian Klein 1 , Candice Jamois 2 , Tina Nielsen 3
ABSTRACT
Introduction
The introduction of anti-CD20 monoclonal antibody therapy with rituximab in the 1990s greatly improved outcomes for patients with B-cell malignancies. Disease resistance or relapse after successful initial therapy and declining efficacy of subsequent rounds of treatment were the basis for the development of alternative anti-CD20-based antibody therapies.
Areas covered
The novel anti-CD20 antibodies of atumumab, ublituximab, and obinutuzumab were developed to be differentiated via structural and mechanistic features over rituximab. We provide an overview of preclinical and clinical data, and demonstrate ways in which the pharmacodynamic properties of these novel agents translate into clinical benefit for patients.
Expert opinion
Of the novel anti-CD20 antibodies, only obinutuzumab has shown consistently improved efficacy over rituximab in randomized pivotal trials in indolent non-Hodgkin lymphoma and chronic lymphocytic leukemia. The Phase 3 GALLIUM trial demonstrated significant improvements in progression-free survival with obinutuzumab-based immunochemotherapy over rituximab-based immunochemotherapy. Novel combinations of obinutuzumab, including with chemotherapy-free options are being explored, such as with the newly approved combinations of obinutuzumab with venetoclax, ibrutinib, or acalabrutinib. The biggest unmet need remains in the treatment of diffuse large B-cell lymphoma; emerging options in this field include the use of CAR-T cells and T-cell bispecific antibodies.
中文翻译:
B细胞恶性肿瘤的抗CD20治疗:现状和未来方向
摘要
介绍
1990 年代引入利妥昔单抗抗 CD20 单克隆抗体治疗极大地改善了 B 细胞恶性肿瘤患者的预后。初始治疗成功后的抗病性或复发以及随后几轮治疗的疗效下降是开发基于抗 CD20 的替代抗体疗法的基础。
涵盖的领域
atumumab、ublituximab 和 obinutuzumab 的新型抗 CD20 抗体被开发为通过结构和机制特征区分利妥昔单抗。我们概述了临床前和临床数据,并展示了这些新型药物的药效学特性如何转化为患者的临床益处。
专家意见
在新型抗 CD20 抗体中,在惰性非霍奇金淋巴瘤和慢性淋巴细胞白血病的随机关键试验中,只有 obinutuzumab 的疗效始终优于利妥昔单抗。3 期 GALLIUM 试验表明,与基于利妥昔单抗的免疫化疗相比,基于 obinutuzumab 的免疫化疗可显着改善无进展生存期。正在探索新的obinutuzumab组合,包括无化疗方案,例如新批准的obinutuzumab与venetoclax、ibrutinib或acalabrutinib的组合。最大的未满足需求仍然是弥漫性大 B 细胞淋巴瘤的治疗;该领域的新兴选择包括使用 CAR-T 细胞和 T 细胞双特异性抗体。