弥漫大 B 细胞淋巴瘤和 B 系急性淋巴细胞白血病患者接受 tisagenlecleucel 后的长期宿主免疫调节

Background: Chimeric antigen receptor (CAR)-T cells represent a potentially curative strategy for patients with relapsed or refractory (R/R) B-cell malignancies. To elucidate a possible host immune activation following CAR-T-cell infusion, we investigated the effects of tisagenlecleucel administration on the patients' immune populations in 25 patients with R/R diffuse large B-cell lymphoma (DLBCL) and B-lineage acute lymphoblastic leukemia (B-ALL). Methods: The modulation of CAR-T cells over time, the numeric changes, as well as the cytokine production capability of different lymphocyte populations and circulating cytokine levels, were analyzed.

Results: Our results confirmed the ability of tisagenlecleucel to control the disease, with an overall response observed in 84. 6% of DLBCL and in 91. 7% of B-ALL patients at 1-month post-infusion, and showed that most patients who subsequently relapsed could undergo further treatment.

Interestingly, we could document a significant increase in CD3 + , CD4 + , CD8 + , and NK cells over time, as well as a decrease in Treg cells, and an increased IFN and TNF production by T lymphocytes. Conclusions: Taken together, our results indicate that in patients with DLBCL and B-ALL, the administration of tisagenlecleucel is capable of inducing a marked and prolonged in vivo modulation/reshaping of the host immune system, both in children and adults.