Nishida Hiroko
Department of Pathology, Keio University, School of Medicine, Tokyo 160-8582, Japan.
Division of Hematology, Department of Internal of Medicine, Keio University, School of Medicine, Tokyo 160-8582, Japan.
Cancers (Basel). 2021 May 31;13(11):2712. doi: 10.3390/cancers13112712.
Despite rapid advances in treatment approaches of multiple myeloma (MM) over the last two decades via proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs), their efficacies are limited. MM still remains incurable, and the majority of patients shortly relapse and eventually become refractory to existing therapies due to the genetic heterogeneity and clonal evolution. Therefore, the development of novel therapeutic strategies with different mechanisms of action represents an unmet need to achieve a deep and highly durable response as well as to improve patient outcomes. The antibody-drug conjugate (ADC), belanatmab mafadotin, which targets B cell membrane antigen (BCMA) on plasma cells, was approved for the treatment of MM in 2020. To date, numerous immunotherapies, including bispecific antibodies, such as bispecific T cell engager (BiTE), the duobody adoptive cellular therapy using a dendritic cell (DC) vaccine, autologous chimeric antigen (CAR)-T cells, allogeneic CAR-natural killer (NK) cells, and checkpoint inhibitors have been developed for the treatment of MM, and a variety of clinical trials are currently underway or are expected to be planned. In the future, the efficacy of combination approaches, as well as allogenic CAR-T or NK cell therapy, will be examined, and promising results may alter the treatment paradigm of MM. This is a comprehensive review with an update on the most recent clinical and preclinical advances with a focus on results from clinical trials in progress with BCMA-targeted immunotherapies and the development of other novel targets in MM. Future perspectives will also be discussed.
尽管在过去二十年中，通过蛋白酶体抑制剂（PIs）、免疫调节药物（IMiDs）和单克隆抗体（mAbs），多发性骨髓瘤（MM）的治疗方法取得了快速进展，但其疗效仍然有限。MM仍然无法治愈，由于基因异质性和克隆进化，大多数患者很快复发，并最终对现有疗法产生耐药性。因此，开发具有不同作用机制的新型治疗策略是实现深度和高度持久缓解以及改善患者预后的未满足需求。靶向浆细胞上B细胞膜抗原（BCMA）的抗体药物偶联物（ADC）——贝兰他单抗马福多汀，于2020年被批准用于治疗MM。迄今为止，已经开发了多种免疫疗法，包括双特异性抗体，如双特异性T细胞衔接器（BiTE）、使用树突状细胞（DC）疫苗的双特异性过继性细胞疗法、自体嵌合抗原受体（CAR）-T细胞、同种异体CAR-自然杀伤（NK）细胞和检查点抑制剂用于治疗MM，目前正在进行或预计将计划开展各种临床试验。未来，将研究联合治疗方法以及同种异体CAR-T或NK细胞疗法的疗效，有前景的结果可能会改变MM的治疗模式。这是一篇全面的综述，更新了最新的临床和临床前进展，重点关注正在进行的针对BCMA的免疫疗法的临床试验结果以及MM中其他新靶点的开发。还将讨论未来的前景。
