Cell Therapy and Transplant Program, Abramson Cancer Center, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.
Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):1-6. doi: 10.1182/hematology.2021000225.
Chimeric antigen receptor T-cell therapy targeting CD19 (CART19) has expanded the treatment options for patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). The approval of tisagenlecleucel for pediatric and young adult patients with r/r ALL has allowed broader access for some patients, but the treatment of older adults is available (at the time of this writing) only within a clinical trial. High remission rates have been consistently observed with varied CART19 products and treatment platforms, but durability of remissions and thus the potential role of a consolidative allogeneic stem cell transplant (SCT) is more uncertain and likely to vary by product and population treated. The immunologic characteristics of CARTs that confer high response rates also account for the life-threatening toxicities of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, the severity of which also varies by patient and disease characteristics and product. Further considerations informing a decision to treat include feasibility of leukapheresis and timeline of manufacture, alternative treatment options available, and the appropriateness of a potential consolidative allogeneic SCT. Advances in the field are under way to improve rate and duration of responses and to mitigate toxicity.
嵌合抗原受体 T 细胞疗法靶向 CD19（CART19）为复发/难治性（r/r）B 细胞急性淋巴细胞白血病（ALL）患者扩大了治疗选择。Tisagenlecleucel 获批准用于 r/r ALL 的儿科和年轻成年患者，使一些患者能够更广泛地获得治疗，但对于老年患者，目前只能在临床试验中获得治疗。不同的 CART19 产品和治疗平台观察到了一致的高缓解率，但缓解的持久性，因此同种异体干细胞移植（SCT）巩固治疗的潜在作用更不确定，可能因产品和治疗人群而异。赋予高反应率的 CART 的免疫特征也导致细胞因子释放综合征和免疫效应细胞相关神经毒性综合征的危及生命的毒性，其严重程度也因患者和疾病特征以及产品而异。进一步决定治疗的考虑因素包括白细胞分离的可行性和制造时间线、可用的替代治疗选择，以及潜在同种异体 SCT 巩固治疗的适当性。该领域正在取得进展，以提高反应率和持续时间，并减轻毒性。
