接受 CD19 CAR-T 治疗的复发/难治性大 B 细胞淋巴瘤患者中欧盟较美国患者结局更差：与肿瘤负荷、全身炎症、桥接治疗使用及 CAR-T 产品使用差异相关

Real-world evidence suggests a trend toward inferior survival of patients receiving CD19 chimeric antigen receptor (CAR) T-cell therapy in Europe (EU) and with tisagenlecleucel. The underlying logistic, patient- and disease-related reasons for these discrepancies remain poorly understood. In this multicenter retrospective observational study, we studied the patient-individual journey from CAR-T indication to infusion, baseline features, and survival outcomes in 374 patients treated with tisagenlecleucel (tisa-cel) or axicabtagene-ciloleucel (axi-cel) in EU and the United States (US).

Compared with US patients, EU patients had prolonged indication-to-infusion intervals (66 versus 50 d; P < 0. 001) and more commonly received intermediary therapies (holding and/or bridging therapy, 94% in EU versus 74% in US; P < 0. 001). Baseline lactate dehydrogenase (LDH) (median 321 versus 271 U/L; P = 0. 02) and ferritin levels (675 versus 425 ng/mL; P = 0. 004) were significantly elevated in the EU cohort.

Overall, we observed inferior survival in EU patients (median progression-free survival [PFS] 3. 1 versus 9. 2 months in US; P < 0. 001) and with tisa-cel (3. 2 versus 9. 2 months with axi-cel; P < 0. 001). On multivariate Lasso modeling, nonresponse to bridging, elevated ferritin, and increased C-reactive protein represented independent risks for treatment failure. Weighing these variables into a patient-individual risk balancer (high risk [HR] balancer), we found higher levels in EU versus US and tisa-cel versus axi-cel cohorts.

Notably, superior PFS with axi-cel was exclusively evident in patients at low risk for progression (according to the HR balancer), but not in high-risk patients. These data demonstrate that inferior survival outcomes in EU patients are associated with longer time-to-infusion intervals, higher tumor burden/LDH levels, increased systemic inflammatory markers, and CAR-T product use.