Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Hashomer, Israel; School of Medicine, Faculty of Medical and health Sciences, Aviv University, Tel-Aviv.
Department of Medicine, Adult Bone Marrow Transplant Service, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine Weill Cornell Medical College, New York.
Haematologica. 2024 Nov 1;109(11):3566-3577. doi: 10.3324/haematol.2023.284664.
The activity of anti-CD19 chimerci antigen receptor (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-Hodgkin 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 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 lactate dehydrogenase, 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.
嵌合抗原受体（CAR）T 细胞治疗抗 CD19 在慢性淋巴细胞白血病（CLL）伴有里希特转化（RT）为侵袭性大 B 细胞淋巴瘤（LBCL）中的活性在很大程度上尚不清楚。在一项多中心回顾性研究中，我们报告了 CAR T 细胞治疗在 RT 患者（N=30）中的安全性和疗效，与侵袭性 B 细胞淋巴瘤患者（N=283）和转化惰性非霍奇金淋巴瘤患者（N=141）进行了比较。在 2016 年 4 月至 2023 年 1 月期间，三分之二的患者在 RT 前接受过 CLL 的治疗，其中 89%的患者接受了 B 细胞受体和 B 细胞淋巴瘤 2 抑制剂的治疗。RT 中 CAR T 细胞治疗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致命毒性。RT 患者的 100 天总缓解率和完全缓解率分别为 57%和 47%。在中位随访 19 个月时，RT 患者的中位总生存期（OS）为 9.9 个月，与新发 LBCL 的 18 个月和转化惰性 NHL 的未达到相比。RT 患者 12 个月的 OS 为 45%，而新发 LBCL 和转化惰性 NHL 患者的 OS 分别为 62%和 75%。在多变量分析中，较差的 OS 与 RT 组织学、乳酸脱氢酶升高和更多的先前治疗线相关。CAR T 细胞治疗可以挽救一部分接受过靶向治疗的 CLL 和 RT 患者；然而，与新发 LBCL 和转化惰性 NHL 相比，RT 的疗效较差。
