Barilà Gregorio, Rizzi Rita, Zambello Renato, Musto Pellegrino
Department of Medicine (DIMED), Hematology and Clinical Immunology Section, Padova University School of Medicine, 35121 Padova, Italy.
Department of Emergency and Organ Transplantation, "Aldo Moro" University School of Medicine, 70121 Bari, Italy.
Pharmaceuticals (Basel). 2021 Jan 7;14(1):40. doi: 10.3390/ph14010040.
The impressive improvement of overall survival in multiple myeloma (MM) patients in the last years has been mostly related to the availability of new classes of drugs with different mechanisms of action, including proteasome inhibitors (PI), immunomodulating agents (IMiDs), and monoclonal antibodies. However, even with this increased potence of fire, MM still remains an incurable condition, due to clonal selection and evolution of neoplastic clone. This concept underlines the importance of immunotherapy as one of the most relevant tools to try to eradicate the disease. In line with this concept, active and passive immunotherapies represent the most attractive approach to this aim. Antibody-drug conjugate(s) (ADCs) and bispecific antibodies (BsAbs) include two innovative tools in order to limit neoplastic plasma cell growth or even, if used at the time of the best response, to potentially eradicate the tumoral clone. Following their promising results as single agent for advanced disease, at the recent 62nd ASH meeting, encouraging data of several combinations, particularly of ADC(s) with PI or IMiDs, have been reported, suggesting even better results for patients treated earlier. In this paper, we reviewed the characteristics, mechanism of action, and clinical data available for most relevant ADC(s) and BsAbs.
近年来,多发性骨髓瘤(MM)患者的总生存期有了显著改善,这主要归功于多种作用机制不同的新型药物的出现,包括蛋白酶体抑制剂(PI)、免疫调节剂(IMiD)和单克隆抗体。然而,即便有了这种更强有力的治疗手段,由于肿瘤克隆的克隆选择和进化,MM仍然是一种无法治愈的疾病。这一概念凸显了免疫疗法作为试图根除该疾病的最相关工具之一的重要性。与此概念一致,主动免疫疗法和被动免疫疗法是实现这一目标最具吸引力的方法。抗体药物偶联物(ADC)和双特异性抗体(BsAb)是两种创新工具,旨在限制肿瘤浆细胞的生长,甚至在最佳反应期使用时,有可能根除肿瘤克隆。在作为晚期疾病的单药治疗取得了令人鼓舞的结果之后,在最近召开的第62届美国血液学会(ASH)会议上,有报道称几种联合用药,特别是ADC与PI或IMiD联合使用,取得了令人鼓舞的数据,这表明早期接受治疗的患者可能会有更好的疗效。在本文中,我们回顾了最相关的ADC和BsAb的特性、作用机制及现有临床数据。