Clinical Research Division and Integrated Immunotherapy Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Medicine, University of Washington, Seattle, Washington.
Am J Hematol. 2019 May;94(S1):S42-S49. doi: 10.1002/ajh.25445. Epub 2019 Mar 6.
CD19-targeted chimeric antigen receptor (CAR)-modified T (CAR-T) cell immunotherapy has demonstrated impressive results in B-cell malignancies, and CAR-T cell therapies targeting other antigens are in development for other cancers. Cytokine release syndrome (CRS) and neurotoxicity can be life-threatening in a subset of patients. The severity of CRS and neurotoxicity can be impacted by the disease burden, lymphodepletion regimen, and CAR-T cell dose. Tocilizumab and corticosteroids have been used to manage these toxicities, enabling CD19 CAR-T cells to be administered without obvious compromise in efficacy. Consensus criteria for grading and managing toxicities will facilitate the widespread application of this treatment modality.
嵌合抗原受体(CAR)修饰的 T(CAR-T)细胞免疫疗法在 B 细胞恶性肿瘤中已显示出显著的疗效,针对其他抗原的 CAR-T 细胞疗法也在开发用于其他癌症。细胞因子释放综合征(CRS)和神经毒性在部分患者中可能有生命危险。CRS 和神经毒性的严重程度可能受到疾病负担、淋巴细胞耗竭方案和 CAR-T 细胞剂量的影响。托珠单抗和皮质类固醇已被用于治疗这些毒性,使 CD19 CAR-T 细胞能够在不明显降低疗效的情况下使用。分级和管理毒性的共识标准将促进这种治疗方式的广泛应用。