Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Scientific Directorate IRCCS of Reggio Emilia, Reggio Emilia, Emilia-Romagna, Italy.
Eur J Haematol. 2024 Mar;112(3):320-327. doi: 10.1111/ejh.14121. Epub 2023 Oct 17.
Multiple myeloma (MM) is an incurable neoplasm characterized by significant morbidity and mortality. Despite advances in treatment, MM patients eventually experienced a relapse of the disease. Penta-drug refractory patients continue to be the hard core of relapsed/refractory (RR) settings. Teclistamab-cqyv is a humanized IgG4 antibody and a bispecific BCMA-director CD3 T-cell engager. It recruits endogenous T cells, by targeting CD3 receptors expressed on their surface, resulting in their activation against BCMA, an antigen expressed by plasma cells. US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved Teclistamab-cqyv in monotherapy for the treatment of RRMM patients who have received at least three prior therapies, including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies (MoAbs) and have demonstrated disease progression during the last therapy. Its effectiveness was demonstrated in a pivotal clinical trial where the overall response rate (ORR) reached 60%. Other clinical studies are currently ongoing to investigate the association of the bispecific antibody with novel drugs with encouraging preliminary results, especially in the setting of heavily pretreated patients. In this review, the authors will provide a comprehensive overview of the drug, including its mechanism of action, major clinical trials, and future perspectives.
多发性骨髓瘤(MM)是一种无法治愈的肿瘤,其特征是发病率和死亡率均较高。尽管治疗取得了进展,但 MM 患者最终仍会复发疾病。五药难治的患者仍然是复发/难治性(RR)环境的核心难点。Teclistamab-cqyv 是一种人源化 IgG4 抗体和双特异性 BCMA 靶向 CD3 T 细胞结合剂。它通过靶向其表面表达的 CD3 受体招募内源性 T 细胞,导致它们针对 BCMA(浆细胞表达的抗原)激活。美国食品和药物管理局(FDA)和欧洲药品管理局(EMA)已批准 Teclistamab-cqyv 单药治疗至少接受过三种先前治疗的 RRMM 患者,包括免疫调节剂(IMiDs)、蛋白酶体抑制剂(PIs)和抗 CD38 单克隆抗体(MoAbs),并且在最后一次治疗期间显示出疾病进展。在一项关键临床试验中,其有效性得到了证实,总缓解率(ORR)达到 60%。目前正在进行其他临床研究,以调查双特异性抗体与新型药物的关联,初步结果令人鼓舞,尤其是在预处理较多的患者中。在这篇综述中,作者将全面概述该药物,包括其作用机制、主要临床试验和未来展望。