Abstract:
Secondary central nervous system (CNS) lymphomas typically require CNS-penetrating drugs; however, the available agents are limited with temporary effects and poor outcomes. Chimeric antigen receptor T (CAR-T) cell therapy (lisocabtagene maraleucel; liso-cel) has been used to treat a few cases of isolated secondary CNS lymphoma. Herein, we report the case of a 66-year-old male diagnosed with diffuse large B-cell lymphoma (Ann Arbor grade IV; R-IPI, good risk; CNS IPI: Intermediate risk) who achieved complete remission (CR) after six courses of R-CHOP therapy. Three months later, he presented with ptosis and eye movement disorder. Systemic CT and bone marrow examination revealed no lymphoma. Although cranial-enhanced MRI showed normal findings, an increased number of B-cells (51/μL) with the original lymphoma phenotype (CD19+CD79a+CD5-CD10-CD20-Igλ+) was detected in cerebrospinal fluid (CSF), indicating an isolated CNS relapse. Seven high-dose methotrexate courses led to partial response. Subsequently, the patient received CAR-T cell therapy with tolerable adverse events - cytokine release syndrome treated with tocilizumab, no immune effector cell-associated neurotoxicity syndrome, and bone marrow failure treated with granulocyte-colony stimulating factor and eltrombopag. Sequential flow cytometry revealed a high peak of CAR-T cells and the presence of residual CAR-T cells in the peripheral blood, indicating immune surveillance of CNS lymphoma by CAR-T cells. This treatment led to a second CR. This case is the first to validate the efficacy and safety of CAR-T cell therapy for isolated secondary CNS lymphoma in clinical practice. Future accumulation of evidence on the efficacy and safety of CAR-T cell therapy is essential.
摘要:
继发性中枢神经系统(CNS)淋巴瘤通常需要中枢神经系统穿透性药物;然而,可用的药物有限,具有暂时性效果和不良结局.嵌合抗原受体T(CAR-T)细胞疗法(liosabtagenemaraleucel;liso-cel)已用于治疗一些孤立的继发性CNS淋巴瘤。在这里,我们报告了一例66岁男性诊断为弥漫性大B细胞淋巴瘤(AnnArborIV级;R-IPI,良好的风险;CNSIPI:中等风险)在六个疗程的R-CHOP治疗后达到完全缓解(CR)。三个月后,他出现了眼睑下垂和眼球运动障碍。全身CT和骨髓检查未发现淋巴瘤。尽管头颅增强MRI显示正常,在脑脊液(CSF)中检测到具有原始淋巴瘤表型(CD19CD79aCD5-CD10-CD20-Igλ)的B细胞(51/μL),表明孤立的中枢神经系统复发。七个高剂量甲氨蝶呤疗程导致部分反应。随后,患者接受有可耐受不良事件的CAR-T细胞疗法-用托珠单抗治疗的细胞因子释放综合征,无免疫效应细胞相关神经毒性综合征,粒细胞集落刺激因子和艾曲波帕治疗骨髓衰竭。序列流式细胞术显示CAR-T细胞的高峰和外周血中残留的CAR-T细胞的存在,表明CAR-T细胞对中枢神经系统淋巴瘤的免疫监视。这种治疗导致第二次CR。该病例首次在临床实践中验证CAR-T细胞疗法治疗孤立性继发性CNS淋巴瘤的有效性和安全性。未来积累有关CAR-T细胞疗法疗效和安全性的证据至关重要。