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 (r/r) B 细胞前体急性淋巴细胞白血病 (B-ALL) 的治疗和结果，但在输注 CAR T 后，通常需要进行干预。在英国的一项多中心研究中，我们回顾性评估了所有符合条件的患者的 tisagenlecleucel 结果，用标准和严格的定义分析了总生存期 (OS) 和无事件生存期 (EFS)，后者包括可测量残留病 (MRD) 的出现和进一步抗-白血病治疗。意向治疗和输注队列均被考虑。我们收集了有关交付、制造、毒性、治疗失败原因的可行性数据，并对患者进行随访直至因任何原因死亡。在 142 名符合条件的患者中，125 名接受 tisagenlecleucel，115/125 (92%) 获得完全缓解 (CR/CRi)。严重细胞因子释放综合征和神经毒性发生率为16/123（13%）和10/123（8.1%），手术死亡率为3/126（2.4%）。 2 年意向治疗 OS 和 EFS 分别为 65.2% (95% CI 57.2–74.2%) 和 46.5% (95% CI 37.6–57.6%)，2 年意向治疗严格 EFS 为 35.6% (95% CI 37.6–57.6%) 28.1–44.9%）。未达到中位 OS。根据严格的事件定义，62 名有反应的患者经历了 CAR T 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)。在全国范围内开展的针对 B-ALL 的 CAR T 细胞疗法的调查，包括对治疗失败后的患者进行随访，为临床医生提供了强有力的结果衡量标准。此前，CAR T 细胞治疗失败后的结果并未得到充分报道。我们的数据表明，在这种情况下，患者可以成功获救，并获得良好的短期生存率。