Portal de Periódicos da CAPES

Inferior Outcomes of EU Versus US Patients Treated With CD19 CAR-T for Relapsed/Refractory Large B-cell Lymphoma: Association With Differences in Tumor Burden, Systemic Inflammation, Bridging Therapy Utilization, and CAR-T Product Use

2023; Wolters Kluwer; Volume: 7; Issue: 8 Linguagem: Inglês

10.1097/hs9.0000000000000907

2572-9241

Veit Bücklein, Ariel Perez Perez, Kai Rejeski, Gloria Iacoboni, Vindi Jurinović, Udo Holtick, Olaf Penack, Soraya Kharboutli, Viktoria Blumenberg, Josephine Ackermann, Lisa Frölich, Grace Johnson, Kedar Patel, Brian Arciola, Rahul Mhaskar, Anthony C. Wood, Christian Schmidt, Omar Albanyan, Philipp Gödel, Eva Hoster, Lars Bullinger, Andréas Mackensen, Frederick L. Locke, Michael von Bergwelt, Pere Barba, Marion Subklewe, Michael D. Jain,

Integrated Circuits and Semiconductor Failure Analysis

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.