Vasudevan Sreeraj, Mohan Lal Bhavesh, Vojjala Nikhil, Mohan Meera
Department of Hematology, Amala Institute of Medical Sciences, Thrissur, India.
Department of Internal Medicine, University of Arkansas for Medical Science, Little Rock, AR, USA.
Expert Opin Biol Ther. 2025 Apr 18:1-7. doi: 10.1080/14712598.2025.2495984.
Bispecific antibodies (bsAbs) have demonstrated impressive standalone effectiveness in relapsed and refractory multiple myeloma, as evidenced by clinical trials and real-world findings. Current clinical studies are investigating these drugs as both monotherapies and in combination treatments for earlier stages of myeloma, including newly diagnosed cases.
With many options available in clinical settings, several questions emerge: How can one bsAb be chosen over another? What is the best way to administer bsAbs, including initial step-up and continuous dosing schedules? How can unique toxicities be managed, and what strategies should be used to address disease relapses following bsAb treatment?
Tocilizumab is being investigated in the prevention of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Steroids can be used to safely treat CRS in myeloma patients on bsAb therapy. This may allow a safe outpatient step-up dosing program. Despite improved infection management with intravenous immunoglobulin prophylaxis, infection risks continue as long as patients are on therapy. This indicates alternative strategies like less frequent dosing or finite duration therapy are needed. Optimal management of disease relapse after bsAb therapy and the sequencing of bsAb and chimeric antigen receptor (CAR) T-cell therapies require further investigation.
双特异性抗体(bsAbs)在复发和难治性多发性骨髓瘤中已显示出令人瞩目的独立疗效,临床试验和真实世界研究结果均证明了这一点。目前的临床研究正在探索将这些药物作为单药疗法以及用于骨髓瘤早期阶段(包括新诊断病例)的联合治疗。
临床环境中有多种选择,随之出现了几个问题:如何在一种双特异性抗体与另一种之间进行选择?双特异性抗体的最佳给药方式是什么,包括初始递增和持续给药方案?如何管理独特的毒性,以及应采用哪些策略来应对双特异性抗体治疗后的疾病复发?
正在研究托珠单抗预防细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)。在接受双特异性抗体治疗的骨髓瘤患者中,类固醇可用于安全治疗CRS。这可能允许一个安全的门诊递增给药方案。尽管通过静脉注射免疫球蛋白预防改善了感染管理,但只要患者接受治疗,感染风险就会持续存在。这表明需要诸如减少给药频率或有限疗程治疗等替代策略。双特异性抗体治疗后疾病复发的最佳管理以及双特异性抗体与嵌合抗原受体(CAR)T细胞疗法的序贯治疗需要进一步研究。