Multiple myeloma is biologically and clinically a complex and heterogeneous disease which develops late in life, with the median age at the time of initial diagnosis being 66 years. In 1975, Durie and Salmon developed the first broadly adopted staging system in multiple myeloma, and in the ensuing decades, the risk stratification tools have improved and now incorporate different parameters to better predict the prognosis and to guide the treatment decisions. The International Staging System (ISS) was initially developed in 2005, revised in 2015 (R-ISS), and again in 2022 (R2-ISS). Tremendous progress has been achieved in multiple myeloma therapy over the past 25 years with the approval of immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies, resulting in a major paradigm shift. The dysfunction of the innate and adaptive immune system, especially in the T cell repertoire, represents a hallmark of multiple myeloma evolution over time, supporting the need for additional therapeutic approaches to activate the host’s immune system and to overcome the immunosuppressive tumor microenvironment. Novel T cell-directed therapies include chimeric antigen receptor (CAR) T cell therapies and bispecific antibodies that leverage the immune system’s T cells to recognize and attack the tumor cells. Second-generation anti-BCMA CAR T cell therapies and bispecific antibodies that bind the tumor antigen BCMA or GPRC5D onto myeloma cells and CD3 on the T cell’s surface are currently available for the treatment of relapsed/refractory multiple myeloma. Despite impressive results obtained with currently approved treatments, multiple myeloma remains incurable, and almost all patients eventually relapse. Moreover, patients with extramedullary disease and plasma cell leukemia represent an unmet medical need that require additional strategies to improve the outcome. In this review, we provide an overview of the evolution of risk stratification and the treatment of multiple myeloma.
多发性骨髓瘤是一种生物学和临床上复杂且异质性的疾病，通常在晚年发病，初次诊断时的中位年龄为66岁。1975年，Durie和Salmon开发了首个被广泛采用的多发性骨髓瘤分期系统。在随后的几十年中，风险分层工具不断改进，现已纳入不同参数以更好地预测预后并指导治疗决策。国际分期系统（ISS）最初于2005年制定，并于2015年修订（R-ISS），2022年再次更新（R2-ISS）。过去25年间，随着免疫调节药物、蛋白酶体抑制剂和抗CD38单克隆抗体的获批，多发性骨髓瘤治疗取得了巨大进展，实现了治疗模式的重大转变。先天性和适应性免疫系统功能障碍，特别是T细胞库的异常，是多发性骨髓瘤进展过程中的标志性特征，这提示需要开发新的治疗方法以激活宿主免疫系统并克服免疫抑制性肿瘤微环境。新型T细胞导向疗法包括嵌合抗原受体（CAR）T细胞疗法和双特异性抗体，这些疗法利用免疫系统的T细胞识别并攻击肿瘤细胞。目前已有第二代靶向BCMA的CAR T细胞疗法及双特异性抗体可用于治疗复发/难治性多发性骨髓瘤，这些疗法通过将肿瘤抗原BCMA或GPRC5D与骨髓瘤细胞结合，同时与T细胞表面的CD3结合发挥作用。尽管现有获批疗法取得了显著疗效，但多发性骨髓瘤仍无法治愈，几乎所有患者最终都会复发。此外，髓外病变和浆细胞白血病患者仍存在未满足的临床需求，需要更多策略来改善其预后。本文综述了多发性骨髓瘤风险分层与治疗策略的演进历程。
肿瘤(癌症)患者之家