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

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Item Type:	Article
Title:	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
Creators Name:	Bücklein, V., Perez, A., Rejeski, K., Iacoboni, G., Jurinovic, V., Holtick, U., Penack, O., Kharboutli, S., Blumenberg, V., Ackermann, J., Frölich, L., Johnson, G., Patel, K., Arciola, B., Mhaskar, R., Wood, A., Schmidt, C., Albanyan, O., Gödel, P., Hoster, E., Bullinger, L., Mackensen, A., Locke, F., von Bergwelt, M., Barba, P., Subklewe, M. and Jain, M.D.
Abstract:	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.
Source:	HemaSphere
ISSN:	2572-9241
Publisher:	Wolters Kluwer
Volume:	7
Number:	8
Page Range:	e907
Date:	August 2023
Official Publication:	https://doi.org/10.1097/hs9.0000000000000907
PubMed:	View item in PubMed

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