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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

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 mu...

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Autores principales: Bücklein, Veit, Perez, Ariel, Rejeski, Kai, Iacoboni, Gloria, Jurinovic, Vindi, Holtick, Udo, Penack, Olaf, Kharboutli, Soraya, Blumenberg, Viktoria, Ackermann, Josephine, Frölich, Lisa, Johnson, Grace, Patel, Kedar, Arciola, Brian, Mhaskar, Rahul, Wood, Anthony, Schmidt, Christian, Albanyan, Omar, Gödel, Philipp, Hoster, Eva, Bullinger, Lars, Mackensen, Andreas, Locke, Frederick, von Bergwelt, Michael, Barba, Pere, Subklewe, Marion, Jain, Michael D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337711/
https://www.ncbi.nlm.nih.gov/pubmed/37449196
http://dx.doi.org/10.1097/HS9.0000000000000907
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author Bücklein, Veit
Perez, Ariel
Rejeski, Kai
Iacoboni, Gloria
Jurinovic, Vindi
Holtick, Udo
Penack, Olaf
Kharboutli, Soraya
Blumenberg, Viktoria
Ackermann, Josephine
Frölich, Lisa
Johnson, Grace
Patel, Kedar
Arciola, Brian
Mhaskar, Rahul
Wood, Anthony
Schmidt, Christian
Albanyan, Omar
Gödel, Philipp
Hoster, Eva
Bullinger, Lars
Mackensen, Andreas
Locke, Frederick
von Bergwelt, Michael
Barba, Pere
Subklewe, Marion
Jain, Michael D.
author_facet Bücklein, Veit
Perez, Ariel
Rejeski, Kai
Iacoboni, Gloria
Jurinovic, Vindi
Holtick, Udo
Penack, Olaf
Kharboutli, Soraya
Blumenberg, Viktoria
Ackermann, Josephine
Frölich, Lisa
Johnson, Grace
Patel, Kedar
Arciola, Brian
Mhaskar, Rahul
Wood, Anthony
Schmidt, Christian
Albanyan, Omar
Gödel, Philipp
Hoster, Eva
Bullinger, Lars
Mackensen, Andreas
Locke, Frederick
von Bergwelt, Michael
Barba, Pere
Subklewe, Marion
Jain, Michael D.
author_sort Bücklein, Veit
collection PubMed
description 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.
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spelling pubmed-103377112023-07-13 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 Bücklein, Veit Perez, Ariel Rejeski, Kai Iacoboni, Gloria Jurinovic, Vindi Holtick, Udo Penack, Olaf Kharboutli, Soraya Blumenberg, Viktoria Ackermann, Josephine Frölich, Lisa Johnson, Grace Patel, Kedar Arciola, Brian Mhaskar, Rahul Wood, Anthony Schmidt, Christian Albanyan, Omar Gödel, Philipp Hoster, Eva Bullinger, Lars Mackensen, Andreas Locke, Frederick von Bergwelt, Michael Barba, Pere Subklewe, Marion Jain, Michael D. Hemasphere Article 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. Lippincott Williams & Wilkins 2023-07-11 /pmc/articles/PMC10337711/ /pubmed/37449196 http://dx.doi.org/10.1097/HS9.0000000000000907 Text en Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Bücklein, Veit
Perez, Ariel
Rejeski, Kai
Iacoboni, Gloria
Jurinovic, Vindi
Holtick, Udo
Penack, Olaf
Kharboutli, Soraya
Blumenberg, Viktoria
Ackermann, Josephine
Frölich, Lisa
Johnson, Grace
Patel, Kedar
Arciola, Brian
Mhaskar, Rahul
Wood, Anthony
Schmidt, Christian
Albanyan, Omar
Gödel, Philipp
Hoster, Eva
Bullinger, Lars
Mackensen, Andreas
Locke, Frederick
von Bergwelt, Michael
Barba, Pere
Subklewe, Marion
Jain, Michael D.
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337711/
https://www.ncbi.nlm.nih.gov/pubmed/37449196
http://dx.doi.org/10.1097/HS9.0000000000000907
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