Tisagenlecleucel 于 2017 年获得美国食品和药物管理局 (FDA) 批准用于治疗难治性 B 细胞急性淋巴细胞白血病 (B-ALL) 和≥2 次复发的 B-ALL。接受商业 tisagenlecleucel 治疗的患者在第一次复发后的结果尚未确定。我们的目的是报告真实世界的 tisagenlecleucel 使用模式和跨适应症的结果，特别是包括第一次复发接受治疗的患者，这是 FDA 正式批准中省略的适应症。我们对 185 名接受治疗的儿童和年轻人的真实世界 tisagenlecleucel 使用模式进行了回顾性分析2017 年 8 月 30 日至 2020 年 3 月 6 日期间，来自美国境内参与儿科真实世界 CAR 联盟 (PRWCC) 的中心。我们描述了现实世界中使用的难治性 B-ALL 的定义，并根据报告的嵌合抗原受体 (CAR) T 细胞适应症对患者进行分类，包括难治性、第一次复发和≥第二次复发 B-ALL。我们分析了定义队列中患者的基线特征和 tisagenlecleucel 治疗后的结果。我们队列中的 36% (n = 67) 在第一次复发后接受了 tisagenlecleucel。在 66 名可评估患者中，56 名（85%，95% CI 74-92%）达到形态学完全缓解。 1 年总生存率 (OS) 和无事件生存率 (EFS) 分别为 69%（95% CI 58-82%）和 49%（95% CI 37-64%），生存结果与其余患者在统计学上具有可比性（OS；p = 0.14，EFS；p = 0.39）。值得注意的是，该队列中的毒性增加，值得进一步研究。有趣的是，在 30 名接受前期难治性疾病治疗的患者中，23 名（77%，95% CI 58-90%）在治疗结束时仅出现流式细胞术和/或下一代测序 (NGS) 最小残留病灶 (MRD) 疾病。诱导，不符合难治性的历史形态学定义。我们的研究结果表明，在接受前期难治性 B-ALL、B-ALL ≥第二次复发和 B-ALL 第一次复发治疗的患者中，tisagenlecleucel 的反应和生存率重叠。我们还强调，难治性 B-ALL 的定义正在超越残留疾病的形态学测量。 Baldrick's/Stand Up 2 Cancer，帕克癌症免疫治疗研究所，弗吉尼亚州和 D.K.路德维希癌症研究基金会。© 2023 作者。

Tisagenlecleucel was approved by the Food and Drug Administration (FDA) in 2017 for refractory B-cell acute lymphoblastic leukemia (B-ALL) and B-ALL in ≥2nd relapse. Outcomes of patients receiving commercial tisagenlecleucel upon 1st relapse have yet to be established. We aimed to report real-world tisagenlecleucel utilisation patterns and outcomes across indications, specifically including patients treated in 1st relapse, an indication omitted from formal FDA approval.We conducted a retrospective analysis of real-world tisagenlecleucel utilisation patterns across 185 children and young adults treated between August 30, 2017 and March 6, 2020 from centres participating in the Pediatric Real-World CAR Consortium (PRWCC), within the United States. We described definitions of refractory B-ALL used in the real-world setting and categorised patients by reported Chimeric Antigen Receptor (CAR) T-cell indication, including refractory, 1st relapse and ≥2nd relapse B-ALL. We analysed baseline patient characteristics and post-tisagenlecleucel outcomes across defined cohorts.Thirty-six percent (n = 67) of our cohort received tisagenlecleucel following 1st relapse. Of 66 evaluable patients, 56 (85%, 95% CI 74-92%) achieved morphologic complete response. Overall-survival (OS) and event-free survival (EFS) at 1-year were 69%, (95% CI 58-82%) and 49%, (95% CI 37-64%), respectively, with survival outcomes statistically comparable to remaining patients (OS; p = 0.14, EFS; p = 0.39). Notably, toxicity was increased in this cohort, warranting further study. Interestingly, of 30 patients treated for upfront refractory disease, 23 (77%, 95% CI 58-90%) had flow cytometry and/or next-generation sequencing (NGS) minimum residual disease (MRD)-only disease at the end of induction, not meeting the historic morphologic definition of refractory.Our findings suggested that tisagenlecleucel response and survival rates overlap across patients treated with upfront refractory B-ALL, B-ALL ≥2nd relapse and B-ALL in 1st relapse. We additionally highlighted that definitions of refractory B-ALL are evolving beyond morphologic measures of residual disease.St. Baldrick's/Stand Up 2 Cancer, Parker Institute for Cancer Immunotherapy, Virginia and D.K. Ludwig Fund for Cancer Research.© 2023 The Authors.