The activity of anti-CD19 CAR T cell therapy in chronic lymphocytic leukemia (CLL) with Richter's transformation (RT) to aggressive large B cell lymphoma (LBCL) is largely unknown. In a multicenter retrospective study, we report the safety and efficacy of CAR T cell therapy in patients with RT (n=30) compared to patients with aggressive B cell lymphoma (n=283) and patients with transformed indolent Non-Hodgkins Lymphoma (iNHL) (n=141) between April 2016 and January 2023. Two-thirds of patients received prior therapy for CLL before RT and 89% of them received B-cell receptor and B-cell lymphoma 2 (BCL-2) inhibitors. Toxicities of CAR T cell therapy in RT were similar to other lymphomas, with no fatalities related to cytokine release syndrome or immune effector-cell associated neurotoxicity synderome. The 100-day overall response rate and complete response rates in patients with RT were 57% and 47%, respectively. With a median follow up of 19 months, the median overall survival (OS) was 9.9 months in patients with RT compared to 18 months in de-novo LBCL and not reached in patients with transformed iNHL. The OS at 12 months was 45% in patients with RT compared with 62% and 75% in patients with de novo LBCL and transformed iNHL, respectively. In a multivariate analysis, worse OS was associated with RT histology, elevated LDH, and more prior lines of therapy. CAR T cell therapy can salvage a proportion of patients with CLL and RT exposed to prior targeted agents; however, efficacy in RT is inferior compared to de novo LBCL and transformed iNHL.

中文翻译：

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抗 CD19 嵌合抗原受体 T 细胞疗法对里氏转化的疗效低于对新生大 B 细胞淋巴瘤和转化的低级别 B 细胞淋巴瘤的疗效。


抗 CD19 CAR T 细胞疗法在慢性淋巴细胞白血病 (CLL) 伴里氏转化 (RT) 至侵袭性大 B 细胞淋巴瘤 (LBCL) 中的活性目前尚不清楚。在一项多中心回顾性研究中，我们报告了与侵袭性 B 细胞淋巴瘤患者 (n=283) 和转化性惰性非霍奇金淋巴瘤 (iNHL) 患者相比，RT 患者 (n=30) 的 CAR T 细胞疗法的安全性和有效性）（n=141）2016 年 4 月至 2023 年 1 月期间。三分之二的患者在 RT 之前接受过 CLL 先前治疗，其中 89% 接受了 B 细胞受体和 B 细胞淋巴瘤 2 (BCL-2) 抑制剂。 RT 中 CAR T 细胞疗法的毒性与其他淋巴瘤相似，没有与细胞因子释放综合征或免疫效应细胞相关神经毒性综合征相关的死亡。 RT患者的100天总缓解率和完全缓解率分别为57%和47%。中位随访时间为 19 个月，RT 患者的中位总生存期 (OS) 为 9.9 个月，而新发 LBCL 患者的中位总生存期 (OS) 为 18 个月，转化 iNHL 患者的中位总生存期 (OS) 未达到。接受 RT 的患者 12 个月的 OS 为 45%，而新发 LBCL 和转化的 iNHL 患者的 12 个月 OS 分别为 62% 和 75%。在多变量分析中，较差的 OS 与 RT 组织学、LDH 升高和更多既往治疗相关。 CAR T 细胞疗法可以挽救一部分接受过既往靶向药物治疗的 CLL 和 RT 患者；然而，与新发 LBCL 和转化的 iNHL 相比，RT 的疗效较差。