Department of Hematology, Centre Hospitalier Universitaire, Nantes, France.
CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, France.
Expert Opin Investig Drugs. 2021 Sep;30(9):965-973. doi: 10.1080/13543784.2021.1955103. Epub 2021 Jul 19.
Multiple myeloma (MM) is still considered incurable and the outcome of patients with triple-class refractory remains very poor. Immunotherapy is considered as a standard of care for the treatment of MM. Among immunotherapeutic approaches, the PD-1/PD-L1 axis is an attractive target because PD-L1 is highly expressed in most myeloma plasma cells. While many types of cancer benefit from checkpoint inhibitor treatment, their relevance in multiple myeloma needs to be defined.
The authors evaluate the published data regarding the mechanism of action, safety profile, and clinical efficacy of the immune checkpoint inhibitors (ICI) for the treatment of multiple myeloma.
The use of ICI monotherapy does not offer any clinical benefit in myeloma patients. In combination with immunomodulatory drugs (IMID), ICI failed to demonstrate clinical benefit and were associated with increased toxicity. Given the toxicities of these treatments, predictive markers would be useful to select patients who would benefit most. Clinical studies are necessary to evaluate the safety and efficacy of checkpoint inhibitors in combination with other standards of care such as proteasome inhibitors and monoclonal antibodies. The combination of anti-PD-1 with T-cell engager (TCE) or CAR-T cells seems theoretically attractive and should be explored in clinical trials.
多发性骨髓瘤（MM）仍然被认为是无法治愈的，三药难治患者的预后仍然非常差。免疫疗法被认为是 MM 治疗的标准护理方法。在免疫治疗方法中，PD-1/PD-L1 轴是一个有吸引力的靶点，因为 PD-L1 在大多数骨髓瘤浆细胞中高度表达。虽然许多类型的癌症受益于检查点抑制剂治疗，但它们在多发性骨髓瘤中的相关性需要进一步明确。
作者评估了关于免疫检查点抑制剂（ICI）治疗多发性骨髓瘤的作用机制、安全性和临床疗效的已发表数据。
ICI 单药治疗在骨髓瘤患者中没有带来任何临床获益。与免疫调节剂（IMID）联合使用，ICI 未能显示出临床获益，且与毒性增加相关。鉴于这些治疗的毒性，预测标志物将有助于选择最受益的患者。有必要开展临床研究来评估检查点抑制剂与蛋白酶体抑制剂和单克隆抗体等其他标准护理方法联合应用的安全性和疗效。抗 PD-1 与 T 细胞衔接器（TCE）或 CAR-T 细胞联合应用在理论上具有吸引力，应在临床试验中进行探索。
