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No free rides: management of toxicities of novel immunotherapies in ALL including financial

机译:禁止搭便车:管理ALL中新型免疫疗法的毒性包括财务管理

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摘要

Therapeutic options for acute lymphoblastic leukemia, especially in the relapsed/refractory setting, have expanded significantly in recent times. However, this comes at the cost of toxicities: medical as well as financial. We highlight some of the unique toxicities associated with the novel agents to apprise our readers about what to expect, how to recognize them, and how to manage these toxicities. One of the toxicities seen with inotuzumab, a CD22 antibody drug conjugate, is sinusoidal obstruction syndrome, which can be fatal in >80% of patients if associated with multiorgan failure. Blinatumomab, a monoclonal antibody targeting CD19, is associated with cytokine release syndrome (CRS) and neurotoxicity, both of which require prompt recognition and management primarily with corticosteroids. CRS and neurotoxicity are more common and more severe with chimeric antigen receptor T-cell therapy (CAR-T). The fact that CAR-T cannot be discontinued on demand adds a layer of complexity to the management of related toxicities of this therapy. Tocilizumab, an interleukin-6 receptor blocker, is used to treat severe CRS from CAR-T, whereas corticosteroids remain the mainstay for neurotoxicity management. Although effective, these drugs carry a high price tag, and we review the available data on cost-effectiveness of these agents, keeping in mind that median follow-up on most of these studies is limited and that long-term data on durability of response remain to be seen.
机译:近年来,尤其是在复发/难治性环境中,急性淋巴细胞白血病的治疗选择已大大扩展。但是,这是以毒性为代价的:医疗和财务方面。我们重点介绍了与新型药物有关的某些独特毒性,以使读者了解预期的结果,如何识别它们以及如何管理这些毒性。与inotuzumab(一种CD22抗体药物结合物)一起看到的毒性之一是窦性阻塞综合征,如果与多器官功能衰竭相关,则可能对80%以上的患者致命。 Blinatumomab是靶向CD19的单克隆抗体,与细胞因子释放综合征(CRS)和神经毒性相关,这两者都需要主要通过皮质类固醇进行迅速识别和处理。嵌合抗原受体T细胞疗法(CAR-T)可使CRS和神经毒性更为常见和严重。 CAR-T不能按需停药的事实为该疗法的相关毒性管理增加了一层复杂性。 Tocilizumab是一种白介素6受体阻滞剂,用于治疗CAR-T引起的严重CRS,而皮质类固醇仍是神经毒性管理的主要手段。这些药物虽然有效,但价格却很高,因此我们回顾了有关这些药物成本效益的可用数据,同时请记住,大多数此类研究的中位随访率有限,并且关于反应持久性的长期数据有待观察。

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