预处理化疗对接受 CAR-T 细胞治疗的 LBCL 患者淋巴细胞动力学及结局的影响

Conditioning chemotherapy (CCT) has been shown to be essential for optimal efficacy of chimeric antigen receptor (CAR) T-cell therapy.

Here, we determined whether the change in absolute lymphocyte count, referred to as delta lymphocyte index (DLIx), may serve as a surrogate marker for pharmacodynamic effects of CCT and whether it associated with germline genetic variants in patients with large B-cell lymphoma (LBCL). One-hundred and seventy-one patients were included, of which 86 (50%) received bridging therapy post-leukapheresis. Median DLIx was 0. 5 10 9 /L (range, 0. 01-2. 75 10 9 /L) and was significantly higher in patients who achieved complete response (p = 0. 04). On multivariate analysis, low DLIx was associated only with use of bridging therapy (odds ratio 0.

4, 95% CI 0. 2-0. 8, p = 0. 007). Low DLIx was independently associated with shorter progression-free (p = 0. 02) and overall survival (p = 0. 02). DLIx was associated with genetic variations related to drug metabolism and macrophage biology such as ABCB1, MISP and CPVL.

The impact of CCT on lymphocyte count is affected by use of bridging therapy but change in lymphocyte count is independently associated with efficacy. Studies aimed at investigating macrophage biology in this setting may suggest strategies to increase the efficacy of CCT and improve outcomes.