Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon, Ehime, 791-0295, Japan.
Division of Immune Regulation, Proteo-Science Center, Ehime University, Toon, Ehime, 791-0295, Japan.
Int J Hematol. 2024 Jul;120(1):23-33. doi: 10.1007/s12185-024-03766-4. Epub 2024 Apr 13.
Despite the development of various therapeutic agents, multiple myeloma remains incurable. Recently, T-cell redirected immunotherapy has become a promising strategy for the treatment of refractory myeloma. Clinical trials using chimeric antigen receptor (CAR)-T cells and bispecific antibodies have demonstrated successful anti-myeloma responses in triple-class-refractory patients. However, unique and unwanted immune effects associated with on-target/off-target reactivity of activated immune cells need to be considered and properly managed. This review summarizes recent advances in bispecific antibodies for the treatment of refractory myeloma. It outlines the history of their development, along with a discussion of their mechanisms of action and their current and potential future role in myeloma therapy. As more evidence emerges to inform the timing of CAR-T-cell therapy, the results of clinical trials and off-the-shelf nature of bispecifics also suggest the timing of their treatment. These findings will promote further development and application of bispecifics for refractory myeloma in combination with other appropriate agents.
尽管已经开发出了各种治疗药物，但多发性骨髓瘤仍然无法治愈。最近，T 细胞导向免疫疗法已成为治疗难治性骨髓瘤的一种有前途的策略。使用嵌合抗原受体 (CAR)-T 细胞和双特异性抗体的临床试验已在三药难治患者中显示出成功的抗骨髓瘤反应。然而，与激活免疫细胞的靶标/非靶标反应相关的独特和不需要的免疫效应需要被考虑并妥善管理。这篇综述总结了用于治疗难治性骨髓瘤的双特异性抗体的最新进展。它概述了它们的发展历史，以及对其作用机制的讨论，以及它们在骨髓瘤治疗中的当前和潜在未来作用。随着更多证据表明 CAR-T 细胞治疗的时机，临床试验的结果和双特异性药物的现货供应性质也表明了它们的治疗时机。这些发现将促进双特异性药物在与其他合适药物联合治疗难治性骨髓瘤方面的进一步发展和应用。
