Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
Department of Internal Medicine II, University Hospital Tuebingen, Tuebingen, Germany.
Transplant Cell Ther. 2023 Dec;29(12):750-756. doi: 10.1016/j.jtct.2023.09.008. Epub 2023 Sep 13.
The outcome of patients with large B cell lymphoma (LBCL) who relapse or progress after CD19-directed chimeric antigen receptor T cell therapy (CAR-T) administered as salvage therapy beyond the second treatment line is poor. However, a minority of patients become long-term survivors despite CAR-T failure. The German Lymphoma Alliance (GLA) has proposed a hierarchical management algorithm for CAR-T failure in LBCL, aimed at allogeneic hematopoietic cell transplantation (alloHCT) as definite therapy in eligible patients. The purpose of this study was to investigate characteristics, relapse patterns, and management strategies in long-term survivors after CAR-T failure, with a particular focus on the feasibility and outcome of alloHCT. This was a retrospective analysis of all evaluable patients with a relapse/progression event (REL) observed in a previously reported GLA sample between November 2018 and May 2021. REL occurred in 214 of 356 patients (60%) who underwent CAR-T for LBCL in the previous GLA study. An evaluable dataset was available for 143 of these 214 patients (67%). Twenty-six of 143 patients (18%) survived 12 months or longer from REL, 109 (76%) died within the first year after REL, and 8 (6%) were alive but had not reached the 12-month landmark. Long-term survivors had more favorable pre-CAR-T features, had a longer interval between CAR-T and REL, and had more often received a tumor biopsy after CAR-T failure, whereas the choice of the first salvage regimen had no impact. AlloHCT was feasible in 40 of 53 patients (75%) intended and resulted in a 12-month post-transplantation overall survival of 36% in those patients who underwent transplantation with sensitive or untreated REL. AlloHCT after CAR-T failure in LBCL is feasible and may be an important contributor to long-term survival, although selection bias must be taken into account. Thus, alloHCT should be considered as a reasonable treatment option for eligible patients in this setting. However, because the overall outlook after CAR-T failure remains poor, novel effective therapeutic approaches are needed, either to allow long-term disease control per se or to improve the preconditions for successful alloHCT.
接受 CD19 导向嵌合抗原受体 T 细胞疗法（CAR-T）作为二线以上挽救疗法治疗后复发或进展的大 B 细胞淋巴瘤（LBCL）患者的结局较差。然而，少数患者尽管 CAR-T 治疗失败仍成为长期幸存者。德国淋巴瘤联盟（GLA）提出了 LBCL 中 CAR-T 失败的分层管理算法，旨在使适合的患者行异基因造血细胞移植（alloHCT）作为确定性治疗。本研究旨在调查 CAR-T 失败后长期幸存者的特征、复发模式和管理策略，特别关注 alloHCT 的可行性和结局。这是对之前报道的 GLA 研究中 2018 年 11 月至 2021 年 5 月间观察到的复发/进展事件（REL）的所有可评估患者进行的回顾性分析。在之前的 GLA 研究中，356 例接受 CAR-T 治疗的 LBCL 患者中 214 例（60%）发生 REL。在这些患者中，143 例有可评估数据集（67%）。在 143 例患者中，有 26 例（18%）自 REL 起 12 个月或更长时间存活，109 例（76%）在 REL 后 1 年内死亡，8 例（6%）存活但未达到 12 个月里程碑。长期幸存者具有更有利的 CAR-T 前特征，CAR-T 与 REL 之间的间隔时间更长，并且在 CAR-T 失败后更常进行肿瘤活检，而首次挽救性治疗方案的选择没有影响。在计划进行 alloHCT 的 53 例患者中，有 40 例（75%）可行，对于敏感或未经治疗的 REL 患者，移植后的 12 个月总生存率为 36%。LBCL 中 CAR-T 失败后的 alloHCT 是可行的，可能是长期生存的重要贡献者，尽管必须考虑选择偏倚。因此，对于这种情况下的适合患者，alloHCT 应被视为合理的治疗选择。然而，由于 CAR-T 失败后的总体预后仍然较差，因此需要新的有效治疗方法，无论是本身实现长期疾病控制还是改善 alloHCT 的成功条件。
