Princess Margaret Cancer Centre, Toronto, ON, Canada.
University of California, San Francisco, San Francisco, CA, USA.
Blood Cancer J. 2024 Sep 12;14(1):158. doi: 10.1038/s41408-024-01139-y.
The treatment paradigm in myeloma is constantly changing. Upfront use of monoclonal antibodies like daratumumab along with proteasome inhibitors (PI)s, and immune modulators (IMiD)s have significantly improved survival and outcomes, but also cause unique challenges at the time of relapse. Engaging immune T cells for tumour cell kill with chimeric antigenic T-cell (CAR T-cell) therapy and bispecific antibodies have become important therapeutic options in relapsed multiple myeloma. Bispecific antibodies are dual antigen targeting constructs that engage the T cells to plasma cells through various target antigens like B-cell membrane antigen (BCMA), G-protein-coupled receptor family C group 5 member D (GPRC5D), and Fc receptor-homolog 5 (FcRH5). These agents have proven to induce deep and durable responses in heavily pre-treated myeloma patients with a predictable safety profile and the ease of off-the-shelf availability. Significant research is ongoing to overcome resistance mechanisms like T cell exhaustion, target antigen mutation or loss and high disease burden. Various trials are also studying these agents as first line options in the newly diagnosed setting. These agents play an important role in the relapsed setting, and efforts are underway to optimize their sequencing in the myeloma treatment algorithm.
骨髓瘤的治疗模式不断变化。在复发时，使用达雷妥尤单抗等单克隆抗体与蛋白酶体抑制剂（PI）和免疫调节剂（IMiD）联合治疗，可以显著提高生存率和治疗效果，但也带来了独特的挑战。嵌合抗原受体 T 细胞（CAR T 细胞）疗法和双特异性抗体通过靶向 B 细胞表面抗原（BCMA）、G 蛋白偶联受体家族 C 组 5 成员 D（GPRC5D）和 Fc 受体同源物 5（FcRH5）等各种靶抗原，激活免疫 T 细胞杀伤肿瘤细胞，已成为复发性多发性骨髓瘤的重要治疗选择。这些药物已被证明可诱导经过大量预处理的骨髓瘤患者产生深度和持久的反应，且具有可预测的安全性和易于获得的优势。目前正在进行大量研究以克服 T 细胞耗竭、靶抗原突变或缺失和高疾病负担等耐药机制。各种试验也在研究这些药物作为新诊断患者的一线治疗选择。这些药物在复发性骨髓瘤治疗中发挥着重要作用，目前正在努力优化其在骨髓瘤治疗方案中的使用顺序。
