CAR T-cell therapy has transformed relapsed/refractory (r/r) B-cell precursor acute lymphoblastic leukaemia (B-ALL) management and outcomes, but following CAR T infusion, interventions are often needed. In a UK multicentre study, we retrospectively evaluated tisagenlecleucel outcomes in all eligible patients, analysing overall survival (OS) and event-free survival (EFS) with standard and stringent definitions, the latter including measurable residual disease (MRD) emergence and further anti-leukaemic therapy. Both intention-to-treat and infused cohorts were considered. We collected data on feasibility of delivery, manufacture, toxicity, cause of therapy failure and followed patients until death from any cause. Of 142 eligible patients, 125 received tisagenlecleucel, 115/125 (92%) achieved complete remission (CR/CRi). Severe cytokine release syndrome and neurotoxicity occurred in 16/123 (13%) and 10/123 (8.1%), procedural mortality was 3/126 (2.4%). The 2-year intent to treat OS and EFS were 65.2% (95%CI 57.2–74.2%) and 46.5% (95%CI 37.6–57.6%), 2-year intent to treat stringent EFS was 35.6% (95%CI 28.1–44.9%). Median OS was not reached. Sixty-two responding patients experienced CAR T failure by the stringent event definition. Post failure, 1-year OS and standard EFS were 61.2% (95%CI 49.3–75.8) and 55.3% (95%CI 43.6–70.2). Investigation of CAR T-cell therapy for B-ALL delivered on a country-wide basis, including following patients beyond therapy failure, provides clinicians with robust outcome measures. Previously, outcomes post CAR T-cell therapy failure were under-reported. Our data show that patients can be successfully salvaged in this context with good short-term survival.
CAR-T细胞疗法已经改变了复发/难治性B细胞前体急性淋巴细胞白血病（B-ALL）的治疗策略与临床结局，但在CAR-T输注后往往仍需进一步干预。在一项英国多中心研究中，我们回顾性评估了所有符合条件的患者接受tisagenlecleucel治疗的结局，采用标准及严格定义分析总生存期（OS）和无事件生存期（EFS），其中严格定义包括可测量残留病（MRD）的出现及后续抗白血病治疗。分析同时覆盖意向治疗人群和实际输注人群。我们收集了治疗实施可行性、制备流程、毒性反应、治疗失败原因等数据，并对患者进行了全因死亡随访。在142例符合条件患者中，125例接受了tisagenlecleucel治疗，其中115/125例（92%）达到完全缓解（CR/CRi）。重度细胞因子释放综合征和神经毒性发生率分别为16/123例（13%）和10/123例（8.1%），治疗相关死亡率为3/126例（2.4%）。意向治疗人群的2年OS和标准EFS分别为65.2%（95%CI 57.2–74.2%）和46.5%（95%CI 37.6–57.6%），严格定义的2年EFS为35.6%（95%CI 28.1–44.9%）。中位OS未达到。根据严格事件定义，62例应答患者出现CAR-T治疗失败。失败后1年OS和标准EFS分别为61.2%（95%CI 49.3–75.8）和55.3%（95%CI 43.6–70.2）。这项全国范围内开展的B-ALL CAR-T细胞疗法研究，涵盖治疗失败后患者的随访，为临床医生提供了可靠的结局评估指标。既往关于CAR-T细胞治疗失败后的结局数据报道不足。我们的数据显示，此类患者仍可获得成功挽救，并实现良好的短期生存。
肿瘤(癌症)患者之家