Division of Hematology, The Ohio State University, Columbus, OH.
Blood Transplant and Cell Therapies Program, Westmead Hospital Department of Haematology, Westmead, NSW, Australia.
J Clin Oncol. 2024 Jun 10;42(17):2071-2079. doi: 10.1200/JCO.24.00033. Epub 2024 Mar 29.
Outcomes for Richter transformation (RT) are poor with current therapies. The efficacy and safety of anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) for RT are not established.
We performed an international multicenter retrospective study of patients with RT who received CAR-T. Patient, disease, and treatment characteristics were summarized using descriptive statistics, and modeling analyses were used to determine association with progression-free survival (PFS) and overall survival (OS). PFS and OS were estimated from the date of CAR-T infusion.
Sixty-nine patients were identified. The median age at CAR-T infusion was 64 years (range, 27-80). Patients had a median of four (range, 1-15) previous lines of therapy for CLL and/or RT, including previous Bruton tyrosine kinase inhibitor and/or BCL2 inhibitor therapy in 58 (84%) patients. The CAR-T product administered was axicabtagene ciloleucel in 44 patients (64%), tisagenlecleucel in 17 patients (25%), lisocabtagene maraleucel in seven patients (10%), and brexucabtagene autoleucel in one patient (1%). Eleven patients (16%) and 25 patients (37%) experienced grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, respectively. The overall response rate was 63%, with 46% attaining a complete response (CR). After a median follow-up of 24 months, the median PFS was 4.7 months (95% CI, 2.0 to 6.9); the 2-year PFS was 29% (95% CI, 18 to 41). The median OS was 8.5 months (95% CI, 5.1 to 25.4); the 2-year OS was 38% (95% CI, 26 to 50). The median duration of response was 27.6 months (95% CI, 14.5 to not reached) for patients achieving CR.
CAR-T demonstrates clinical efficacy for patients with RT.
目前的治疗方法对 Richter 转化（RT）的疗效不佳。抗 CD19 嵌合抗原受体 T 细胞疗法（CAR-T）治疗 RT 的疗效和安全性尚未确定。
我们对接受 CAR-T 的 RT 患者进行了一项国际多中心回顾性研究。使用描述性统计方法总结患者、疾病和治疗特征，并进行建模分析以确定与无进展生存期（PFS）和总生存期（OS）的关联。PFS 和 OS 从 CAR-T 输注日期开始估计。
确定了 69 例患者。CAR-T 输注时的中位年龄为 64 岁（范围，27-80）。患者中位接受了四种（范围，1-15）针对 CLL 和/或 RT 的既往治疗线，58（84%）例患者接受了先前的布鲁顿酪氨酸激酶抑制剂和/或 BCL2 抑制剂治疗。给予的 CAR-T 产品为 axicabtagene ciloleucel（44 例，64%）、tisagenlecleucel（17 例，25%）、lisocabtagene maraleucel（7 例，10%）和 brexucabtagene autoleucel（1 例，1%）。11 例（16%）和 25 例（37%）患者分别发生了≥3 级细胞因子释放综合征和免疫效应细胞相关神经毒性综合征。总体缓解率为 63%，其中 46%达到完全缓解（CR）。中位随访 24 个月后，中位 PFS 为 4.7 个月（95%CI，2.0 至 6.9）；2 年 PFS 为 29%（95%CI，18 至 41）。中位 OS 为 8.5 个月（95%CI，5.1 至 25.4）；2 年 OS 为 38%（95%CI，26 至 50）。达到 CR 的患者的中位缓解持续时间为 27.6 个月（95%CI，14.5 至未达到）。
CAR-T 对 RT 患者具有临床疗效。
