Division of Hematology, Mayo Clinic, Rochester, MN, United States.
Division of Hematology, St Vincent's Hospital Melbourne, Melbourne, VIC, Australia.
Front Immunol. 2024 Oct 10;15:1424925. doi: 10.3389/fimmu.2024.1424925. eCollection 2024.
Recently, several bispecific antibodies (BsAbs) have been approved for the treatment of relapsed multiple myeloma (MM) after early phase trials in heavily pre-treated patients demonstrated high response rates and impressive progression-free survival with monotherapy. These BsAbs provide crucial treatment options for relapsed patients and challenging decisions for clinicians. Evidence on the optimal patient population, treatment sequence, and duration of these therapeutics is unknown and subject to active investigation. While rates of cytokine release syndrome and neurotoxicity appear to be lower with BsAbs than with CAR T-cells, morbidity from infection is high and novel pathways of treatment resistance arise from the longitudinal selection pressure of chronic BsAb therapy. Lastly, a wealth of novel T-cell engagers with unique antibody-structures and antigenic targets are under active investigation with promising early outcome data. In this review, we examine the mechanism of action, therapeutic targets, combinational approaches, sequencing and mechanisms of disease relapse for BsAbs in MM.
最近，在经过早期临床试验后，几种双特异性抗体（BsAbs）已被批准用于治疗多发性骨髓瘤（MM）的复发，这些临床试验显示，在经过大量预处理的患者中，BsAbs 单药治疗具有较高的缓解率和令人印象深刻的无进展生存期。这些 BsAbs 为复发患者提供了重要的治疗选择，并给临床医生带来了困难的决策。对于这些治疗方法的最佳患者人群、治疗顺序和持续时间的证据尚不清楚，目前正在积极研究中。虽然 BsAbs 引起细胞因子释放综合征和神经毒性的发生率似乎低于 CAR T 细胞，但感染的发病率很高，并且由于慢性 BsAb 治疗的纵向选择压力，会出现新的治疗耐药途径。最后，大量具有独特抗体结构和抗原靶点的新型 T 细胞激动剂正在积极研究中，早期结果数据令人鼓舞。在这篇综述中，我们研究了 BsAbs 在 MM 中的作用机制、治疗靶点、联合治疗方法、序贯治疗和疾病复发的机制。
