Department of Hematology, Singapore General Hospital, Singapore, Singapore -
SingHealth Duke NUS Blood Cancer Center, Singapore, Singapore -
Panminerva Med. 2021 Mar;63(1):28-36. doi: 10.23736/S0031-0808.20.04121-X. Epub 2020 Sep 21.
Recent advances in treatment modalities have led to improved survival in patients with multiple myeloma (MM). However, despite these, MM remains an incurable disease. Many MM patients relapse through and become refractory to current treatment strategies or are intolerant due to toxicities arising from therapy. As such, novel strategies addressing new targets are crucial in improving care for MM patients. BCMA has emerged as a rationale therapeutic target for treatment of MM as it is preferentially expressed in mature B-lymphocytes and plasma cells with the overexpression and activation of BCMA via its ligands associated with the disease progression in multiple myeloma. Given the high expression of BCMA in malignant Plasma cells compared to those from normal healthy volunteers, targeting BCMA should reduce risks of on-target off-tumor toxicities. The main BCMA-targeting approaches currently used for treatment of MM include: 1) chimeric antigen receptor (CAR) T-cell therapy; 2) bi- and multi- specific antibodies; and 3) monoclonal antibodies and their drug conjugates. This review will outline these therapeutic agents and present their emerging clinical data.
近年来,治疗方式的进步使得多发性骨髓瘤(MM)患者的生存率得到了提高。然而,尽管如此,MM 仍然是一种无法治愈的疾病。许多 MM 患者通过复发对当前的治疗策略产生耐药性,或者由于治疗引起的毒性而无法耐受。因此,针对新靶点的新策略对于改善 MM 患者的治疗至关重要。BCMA 已成为 MM 治疗的合理治疗靶点,因为它在成熟的 B 淋巴细胞和浆细胞中优先表达,并且通过其配体的过度表达和激活与多发性骨髓瘤的疾病进展相关。鉴于恶性浆细胞中 BCMA 的高表达与正常健康志愿者相比,靶向 BCMA 应该降低脱靶肿瘤毒性的风险。目前用于治疗 MM 的主要 BCMA 靶向方法包括:1)嵌合抗原受体(CAR)T 细胞疗法;2)双特异性和多特异性抗体;3)单克隆抗体及其药物偶联物。这篇综述将概述这些治疗药物,并介绍它们新出现的临床数据。