Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
Division of Hospital Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
Transplant Cell Ther. 2022 Jun;28(6):342.e1-342.e5. doi: 10.1016/j.jtct.2022.02.021. Epub 2022 Mar 4.
Anti-CD19 chimeric antigen receptor T cell therapy (CAR19) represents a critical treatment modality for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, the majority of patients subsequently experience disease progression following CAR19, and data are limited on assessing the best salvage regimen for these patients. This study aimed to evaluate outcomes in R/R DLBCL patients with progressive disease post-CAR19 and to assess variables that predict response to salvage therapy. We performed a retrospective analysis of all patients with DLBCL who received CAR19 at our institution between January 2018 and February 2021, collecting data on demographic characteristics, disease characteristics, best response to CAR19, date of relapse or progression, and first salvage therapy and response to salvage. We analyzed patients according to whether they responded to CAR19 (responders) or did not (nonresponders). Salvage regimens were classified into 6 groups for analysis. Primary endpoints included overall survival (OS) and progression-free survival (PFS), calculated using the Kaplan-Meier method. Cox models were fit to evaluate the effect of prognostic factors. Among the 120 patients who received CAR19 during the analysis period were 69 responders who achieved a complete or partial response to CAR19 and 51 nonresponders, including 44 with stable or progressive disease and 7 who died before assessment. Thirty responders relapsed and 26 received salvage therapy, and 24 nonresponders received salvage therapy. The primary salvage regimens included lenalidomide-based regimens (n = 17; 34%), BTKi (n = 10; 20%), checkpoint inhibitor-based (n = 7; 14%), chemo-immunotherapy (n = 5; 10%), allogeneic hematopoietic stem cell transplantation (n = 5; 10%), and others (n = 6; 12%). There was no significant difference in OS based on salvage regimen (P = .4545). Responders who received salvage therapy had significantly longer OS than nonresponders (median OS not reached versus 10.9 months; P = .0187), and response to CAR19 and elevated lactate dehydrogenase level at time of salvage treatment were the only two statistically significant prognostic factors after accounting for other variables. Responders to CAR19 had significantly better outcomes with salvage therapy compared with nonresponders to CAR19. There was no significant difference in outcomes based on salvage regimen. Future research is needed to assess the best salvage regimen post-CAR19 failure.
抗 CD19 嵌合抗原受体 T 细胞疗法（CAR19）是治疗复发/难治性（R/R）弥漫性大 B 细胞淋巴瘤（DLBCL）患者的重要治疗方法。然而，大多数患者在接受 CAR19 治疗后会出现疾病进展，并且关于评估这些患者最佳挽救治疗方案的数据有限。本研究旨在评估 CAR19 后疾病进展的 R/R DLBCL 患者的结局，并评估预测挽救治疗反应的变量。我们对 2018 年 1 月至 2021 年 2 月在我院接受 CAR19 治疗的所有 DLBCL 患者进行了回顾性分析，收集了患者的人口统计学特征、疾病特征、对 CAR19 的最佳反应、复发或进展的日期以及首次挽救治疗和对挽救治疗的反应等数据。我们根据患者对 CAR19 的反应（应答者）或无反应（无应答者）进行了分析。挽救治疗方案分为 6 组进行分析。主要终点包括使用 Kaplan-Meier 法计算的总生存期（OS）和无进展生存期（PFS）。Cox 模型用于评估预后因素的影响。在分析期间接受 CAR19 治疗的 120 名患者中，有 69 名应答者对 CAR19 达到完全或部分缓解，51 名无应答者，其中 44 名患者疾病稳定或进展，7 名患者在评估前死亡。30 名应答者复发，26 名接受挽救治疗，24 名无应答者接受挽救治疗。主要挽救治疗方案包括基于来那度胺的方案（n=17；34%）、BTKi（n=10；20%）、基于检查点抑制剂的方案（n=7；14%）、化疗免疫治疗（n=5；10%）、异基因造血干细胞移植（n=5；10%）和其他（n=6；12%）。挽救治疗方案之间的 OS 无显著差异（P=0.4545）。接受挽救治疗的应答者的 OS 明显长于无应答者（中位 OS 未达到与 10.9 个月；P=0.0187），并且在考虑其他变量后，CAR19 的应答和挽救治疗时升高的乳酸脱氢酶水平是唯一两个具有统计学意义的预后因素。与 CAR19 无应答者相比，CAR19 应答者接受挽救治疗的结局显著更好。挽救治疗方案之间的结局无显著差异。需要进一步研究以评估 CAR19 失败后的最佳挽救治疗方案。
