Jain Tania, Litzow Mark R
Hematologic Malignancies and Bone Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, 3M88, Baltimore, MD 21287, USA.
Division of Hematology and Bone Marrow Transplant, Mayo Clinic, Rochester, MN, USA.
Ther Adv Hematol. 2020 Jan 20;11:2040620719899897. doi: 10.1177/2040620719899897. eCollection 2020.
The advent of novel immunotherapies, such as blinatumomab, inotuzumab, and chimeric antigen receptor (CAR) T cell therapy, has revolutionized the therapeutic landscape in the treatment of relapsed/refractory B cell acute lymphoblastic leukemia, but can be associated with specific toxicities. We review unique toxicities of each of these in this article. Blinatumomab, a bispecific T cell engager, has been associated with cytokine release syndrome (CRS) and neurological toxicities, both of which can be prevented and managed with corticosteroids. Inotuzumab is a calicheamicin-conjugated CD22 targeting antibody. The calicheamicin component of the drug is likely associated with the hepatotoxicity seen with inotuzumab, especially sinusoidal obstruction syndrome, which can happen both in the context of the drug alone, and also with allogeneic stem cell transplantation. QT prolongation has also been noted with inotuzumab. CAR T therapy uses genetically modified autologous T cells directed against CD19, a known target on B cells. CRS and neurological symptoms, formally termed as immune-effector-cell-associated neurological syndrome, have been described along with hypogammaglobulinemia, cytopenias, and infections.
新型免疫疗法的出现，如双特异性T细胞衔接器博纳吐单抗、伊尼妥单抗和嵌合抗原受体（CAR）T细胞疗法，彻底改变了复发/难治性B细胞急性淋巴细胞白血病的治疗格局，但可能伴有特定毒性。我们在本文中回顾了每种疗法的独特毒性。博纳吐单抗作为一种双特异性T细胞衔接器，与细胞因子释放综合征（CRS）和神经毒性有关，这两种毒性都可以用皮质类固醇预防和处理。伊尼妥单抗是一种与加利车霉素偶联的靶向CD22的抗体。该药物的加利车霉素成分可能与伊尼妥单抗所致的肝毒性有关，尤其是窦性阻塞综合征，这在单独使用该药物以及异基因干细胞移植的情况下都可能发生。伊尼妥单抗还可引起QT间期延长。CAR T疗法使用针对B细胞上已知靶点CD19的基因改造自体T细胞。已报道了CRS和神经症状，正式名称为免疫效应细胞相关神经综合征，同时还有低丙种球蛋白血症、血细胞减少和感染。
