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

Preview	PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader 5MB
	Other (Supplemental Material) 2MB

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. and Perez, A. and Rejeski, K. and Iacoboni, G. and Jurinovic, V. and Holtick, U. and Penack, O. and Kharboutli, S. and Blumenberg, V. and Ackermann, J. and Frölich, L. and Johnson, G. and Patel, K. and Arciola, B. and Mhaskar, R. and Wood, A. and Schmidt, C. and Albanyan, O. and Gödel, P. and Hoster, E. and Bullinger, L. and Mackensen, A. and Locke, F. and von Bergwelt, M. and Barba, P. and 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

Repository Staff Only: item control page

Download Statistics

Download Statistics

Download Statistics

Downloads

Downloads per month over past year