Lombardi Comprehensive Cancer Center and MedStar Georgetown University Hospital, Washington, DC.
Dahlgren Memorial Library, Georgetown University, Washington, DC.
Blood Adv. 2023 Jan 10;7(1):32-39. doi: 10.1182/bloodadvances.2022008525.
Relapsed/refractory primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) are associated with short survival and represent an unmet need, requiring novel effective strategies. Anti-CD19 chimeric antigen receptor (CAR) T cells, effective in systemic large B-cell lymphoma (LBCL), have shown responses in PCNSL and SCNSL in early reports, but with limited sample size. We, therefore, performed a comprehensive systematic review and meta-analysis of all published data describing CAR T-cell use in PCNSL and SCNSL. This identified 128 patients with PCNSL (30) and SCNSL (98). Our primary objectives were to evaluate CAR T-cell specific toxicity (immune effector cell-associated neurotoxicity syndrome [ICANS] and cytokine release syndrome [CRS]) as well as response rates in these 2 populations. Seventy percent of patients with PCNSL had CRS of any grade (13% grade 3-4) and 53% had ICANS of any grade (18% grade 3-4). Comparatively, 72% of the SCNSL cohort experienced CRS of any grade (11% grade 3-4) and 48% had ICANS of any grade (26% grade 3-4). Of the patients with PCNSL, 56% achieved a complete remission (CR) with 37% remaining in remission at 6 months. Similarly, 47% of patients with SCNSL had a CR, with 37% in remission at 6 months. In a large meta-analysis of central nervous system (CNS) lymphomas, toxicity of anti-CD19-CAR T-cell therapy was similar to that of registrational studies in systemic LBCL with no increased signal of neurotoxicity observed. Encouraging efficacy was demonstrated in patients with CNS lymphoma with no discernible differences between PCNSL and SCNSL.
原发性中枢神经系统淋巴瘤（PCNSL）和继发性中枢神经系统淋巴瘤（SCNSL）缓解后复发或难治，生存时间短，存在未满足的需求，需要新的有效治疗策略。抗 CD19 嵌合抗原受体（CAR）T 细胞在系统性大 B 细胞淋巴瘤（LBCL）中有效，早期报告显示其在 PCNSL 和 SCNSL 中有反应，但样本量有限。因此，我们对所有描述 CAR T 细胞在 PCNSL 和 SCNSL 中应用的已发表数据进行了全面的系统评价和荟萃分析。这确定了 128 例 PCNSL（30 例）和 SCNSL（98 例）患者。我们的主要目标是评估这 2 个人群中 CAR T 细胞特有的毒性（免疫效应细胞相关神经毒性综合征 [ICANS]和细胞因子释放综合征 [CRS]）和反应率。70%的 PCNSL 患者有任何级别（13%为 3-4 级）的 CRS，53%的患者有任何级别（18%为 3-4 级）的 ICANS。相比之下，72%的 SCNSL 患者有任何级别的 CRS（11%为 3-4 级），48%的患者有任何级别的 ICANS（26%为 3-4 级）。在 PCNSL 患者中，56%的患者达到完全缓解（CR），37%的患者在 6 个月时仍处于缓解状态。同样，47%的 SCNSL 患者有 CR，37%的患者在 6 个月时处于缓解状态。在一项对中枢神经系统（CNS）淋巴瘤的大型荟萃分析中，抗 CD19-CAR T 细胞治疗的毒性与系统性 LBCL 注册研究相似，没有观察到神经毒性信号增加。在 CNS 淋巴瘤患者中，疗效令人鼓舞，PCNSL 和 SCNSL 之间没有明显差异。
