Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Nat Med. 2024 Apr;30(4):984-989. doi: 10.1038/s41591-024-02826-w. Epub 2024 Jan 24.
We report a T cell lymphoma (TCL) occurring 3 months after anti-CD19 chimeric antigen receptor (CAR) T cell immunotherapy for non-Hodgkin B cell lymphoma. The TCL was diagnosed from a thoracic lymph node upon surgery for lung cancer. The TCL exhibited CD8 cytotoxic phenotype and a JAK3 variant, while the CAR transgene was very low. The T cell clone was identified at low levels in the blood before CAR T infusion and in lung cancer. To assess the overall risk of secondary primary malignancy after commercial CAR T (CD19, BCMA), we analyzed 449 patients treated at the University of Pennsylvania. At a median follow-up of 10.3 months, 16 patients (3.6%) had a secondary primary malignancy. The median onset time was 26.4 and 9.7 months for solid and hematological malignancies, respectively. The projected 5-year cumulative incidence is 15.2% for solid and 2.3% for hematological malignancies. Overall, one case of TCL was observed, suggesting a low risk of TCL after CAR T.
我们报告了一例发生在非霍奇金 B 细胞淋巴瘤抗 CD19 嵌合抗原受体(CAR)T 细胞免疫治疗后 3 个月的 T 细胞淋巴瘤(TCL)。该 TCL 是在肺癌手术时从胸淋巴结中诊断出来的。TCL 表现出 CD8 细胞毒性表型和 JAK3 变异,而 CAR 转基因非常低。在 CAR T 输注前和肺癌患者的血液中,该 T 细胞克隆的水平较低。为了评估商业 CAR T(CD19、BCMA)治疗后发生继发性原发性恶性肿瘤的总体风险,我们分析了宾夕法尼亚大学 449 名患者的数据。中位随访 10.3 个月时,16 名患者(3.6%)发生了继发性原发性恶性肿瘤。实体瘤和血液系统恶性肿瘤的中位发病时间分别为 26.4 个月和 9.7 个月。预计 5 年累积发病率分别为 15.2%和 2.3%。总体而言,观察到 1 例 TCL,提示 CAR T 后 TCL 的风险较低。