Faculty of Medicine, Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.
Faculty of Medicine, Department of Hematology, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.
Br J Haematol. 2023 Jul;202(1):74-85. doi: 10.1111/bjh.18816. Epub 2023 Apr 18.
Chimeric antigen receptor (CAR) T cells targeted to the CD19 B-cell antigen form an approved treatment for patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). However, since this therapy is administered after multiple lines of treatment and exposure to lymphotoxic agents, there is an urgent need to optimize this modality of treatment.
To circumvent the difficulties of harvesting adequate and optimal T cells from DLBCL patients and improve CART therapy, we suggest an earlier lymphopheresis (i.e. at first relapse, before salvage treatment). We conducted a prospective study and evaluated the potential benefit of an earlier lymphopheresis (early group, n = 22) on the clinical outcome of CD19-CART infused DLBCL patients, in comparison with standard lymphopheresis (i.e. at second relapse and beyond; standard group, n = 23).
An increased percentage of naïve T cells and increased in vitro T-cell functionality were observed in the early group. Additionally, these cells exhibit a lower exhaustion profile than T cells collected in the standard group.
While improved T-cell phenotype and function in the lymphopheresis product did not translate into significantly improved clinical outcomes, a trend towards better overall survival (OS) and progression-free survival (PFS) was observed. Early lymphopheresis maximizes the potential of salvage therapies, without compromising CAR T-cell quality.
靶向 CD19 B 细胞抗原的嵌合抗原受体 (CAR) T 细胞已被批准用于治疗复发/难治性弥漫性大 B 细胞淋巴瘤 (r/r DLBCL) 患者。然而，由于这种治疗方法是在多次治疗和接触淋巴毒性药物后进行的，因此迫切需要优化这种治疗方式。
为了克服从 DLBCL 患者中采集足够和最佳 T 细胞的困难，并改善 CART 治疗，我们建议更早进行淋巴细胞清除术（即在首次复发时，在挽救治疗之前）。我们进行了一项前瞻性研究，评估了早期淋巴细胞清除术（早期组，n=22）对输注 CD19-CART 的 DLBCL 患者临床结局的潜在益处，并与标准淋巴细胞清除术（即第二次复发及以后；标准组，n=23）进行了比较。
早期组观察到幼稚 T 细胞的百分比增加和体外 T 细胞功能增强。此外，与标准组采集的 T 细胞相比，这些细胞表现出较低的衰竭特征。
尽管淋巴细胞清除术产物中 T 细胞表型和功能的改善并未转化为显著改善的临床结局，但观察到总生存期（OS）和无进展生存期（PFS）的趋势更好。早期淋巴细胞清除术最大限度地提高了挽救治疗的潜力，同时不影响 CAR T 细胞的质量。
