Chimeric antigen receptor (CAR) T‐cell therapy has revolutionized treatment of aggressive large B‐cell lymphoma (aLBCL). Patients with transformed indolent non‐Hodgkin lymphoma (tiNHL) were included in key CAR trials, but outcomes of CAR for this distinct, historically high‐risk group are poorly understood. We conducted a multicenter retrospective study of 1182 patients with aLBCL receiving standard‐of‐care CAR T between 2017 and 2022, including 338 (29%) with tiNHL. Rates of grade ≥ 3 cytokine release syndrome (CRS) were similar between tiNHL and de novo cohorts (7% vs. 8%, p = 0.6), while grade ≥ 3 immune effector cell‐associated neurotoxicity syndrome was lower in tiNHL (21% vs. 27%, p = 0.02). Overall response rate was similar in both cohorts (83% vs. 81%, p = 0.3), while complete response rate was higher in tiNHL (67% vs. 59%, p = 0.017). With a median follow‐up of 22.3 months, the progression/relapse‐free (PFS) and overall survival (OS) were similar between the tiNHL and de novo cohorts (24‐month PFS 41% [95% CI: 35%–46%] vs. 38% [95% CI: 35%–42%]; 24‐month OS 58% [95% CI: 52%–63%] vs. 52% [95% CI: 48%–56%], respectively). After adjusting for key risk factors, there was a trend toward a lower hazard of disease progression, relapse or death post‐CAR for tiNHL patients compared to de novo aLBCL patients (HR: 0.84 [95% CI: 0.69–1.0], p = 0.07). Elevated LDH, advanced stage, prior bendamustine within 12 months of CAR, receipt of bridging therapy, CNS involvement, and ≥ 3 prior lines of therapy were each associated with inferior PFS. In conclusion, CAR T therapy is highly effective with an acceptable toxicity profile in patients with tiNHL.

中文翻译：

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CD19 CAR T 在转化惰性淋巴瘤中与新发侵袭性大 B 细胞淋巴瘤相比的结局


嵌合抗原受体 （CAR） T 细胞疗法彻底改变了侵袭性大 B 细胞淋巴瘤 （aLBCL） 的治疗。转化惰性非霍奇金淋巴瘤 （tiNHL） 患者被纳入关键的 CAR 试验，但对这一独特的、历史上高危人群的 CAR 结局知之甚少。我们对 2017 年至 2022 年间接受标准护理 CAR T 的 1182 名 aLBCL 患者进行了一项多中心回顾性研究，其中包括 338 名 （29%） 患有 tiNHL。tiNHL 队列和新发队列之间 ≥ 级细胞因子释放综合征 （CRS） 的发生率相似 （7% vs. 8%，p = 0.6），而 ≥ 级免疫效应细胞相关神经毒性综合征在 tiNHL 中较低 （21% vs. 27%，p = 0.02）。两个队列的总体缓解率相似 （83% vs. 81%，p = 0.3），而 tiNHL 的完全缓解率更高 （67% vs. 59%，p = 0.017）。中位随访 22.3 个月，tiNHL 和新发队列之间的进展/无复发 （PFS） 和总生存期 （OS） 相似（24 个月 PFS 41% [95% CI：35%–46%] vs. 38% [95% CI： 35%–42%];24 个月 OS 分别为 58% [95% CI： 52%–63%] vs. 52% [95% CI： 48%–56%]）。在调整了关键危险因素后，与新发 aLBCL 患者相比，tiNHL 患者在 CAR 后疾病进展、复发或死亡的风险有降低的趋势 （HR： 0.84 [95% CI： 0.69–1.0]，p = 0.07）。LDH 升高、晚期、CAR 后 12 个月内既往苯达莫司汀、接受桥接治疗、CNS 受累以及≥ 3 线治疗均与较差的 PFS 相关。总之，CAR T 疗法对 tiNHL 患者非常有效，毒性可接受。