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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-08-01
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| Series: | HemaSphere |
| Online Access: | http://journals.lww.com/10.1097/HS9.0000000000000907 |
| _version_ | 1797281628145319936 |
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| author | Veit Bücklein Ariel Perez Kai Rejeski Gloria Iacoboni Vindi Jurinovic Udo Holtick Olaf Penack Soraya Kharboutli Viktoria Blumenberg Josephine Ackermann Lisa Frölich Grace Johnson Kedar Patel Brian Arciola Rahul Mhaskar Anthony Wood Christian Schmidt Omar Albanyan Philipp Gödel Eva Hoster Lars Bullinger Andreas Mackensen Frederick Locke Michael von Bergwelt Pere Barba Marion Subklewe Michael D. Jain |
| author_facet | Veit Bücklein Ariel Perez Kai Rejeski Gloria Iacoboni Vindi Jurinovic Udo Holtick Olaf Penack Soraya Kharboutli Viktoria Blumenberg Josephine Ackermann Lisa Frölich Grace Johnson Kedar Patel Brian Arciola Rahul Mhaskar Anthony Wood Christian Schmidt Omar Albanyan Philipp Gödel Eva Hoster Lars Bullinger Andreas Mackensen Frederick Locke Michael von Bergwelt Pere Barba Marion Subklewe Michael D. Jain |
| author_sort | Veit Bücklein |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-07T17:00:10Z |
| format | Article |
| id | doaj.art-96c7942628c54f0395c416764e463604 |
| institution | Directory Open Access Journal |
| issn | 2572-9241 |
| language | English |
| last_indexed | 2024-03-07T17:00:10Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj.art-96c7942628c54f0395c416764e4636042024-03-03T03:25:44ZengWileyHemaSphere2572-92412023-08-0178e90710.1097/HS9.0000000000000907202308000-00002Inferior 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 UseVeit Bücklein0Ariel Perez1Kai Rejeski2Gloria Iacoboni3Vindi Jurinovic4Udo Holtick5Olaf Penack6Soraya Kharboutli7Viktoria Blumenberg8Josephine Ackermann9Lisa Frölich10Grace Johnson11Kedar Patel12Brian Arciola13Rahul Mhaskar14Anthony Wood15Christian Schmidt16Omar Albanyan17Philipp Gödel18Eva Hoster19Lars Bullinger20Andreas Mackensen21Frederick Locke22Michael von Bergwelt23Pere Barba24Marion Subklewe25Michael D. Jain261 Department of Medicine III, University Hospital, LMU Munich, Germany3 Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA1 Department of Medicine III, University Hospital, LMU Munich, Germany6 Department of Hematology, Vall d’Hebron Institute of Oncology (VHIO), University Hospital Vall d’Hebron, Department of Medicine, Universitat Autònoma of Barcelona (UAB), Spain7 Institute for Medical Information Processing, Biometry, and Epidemiology, LMU Munich, Germany8 Department I of Internal Medicine, Medical Faculty and University Hospital, Cologne, University of Cologne, Germany9 Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Tumorimmunology, Berlin, Germany10 Department of Internal Medicine 5, Hematology and Oncology, University of Erlangen-Nuremberg, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany1 Department of Medicine III, University Hospital, LMU Munich, Germany11 USF Health Morsani College of Medicine, Tampa, FL, USA11 USF Health Morsani College of Medicine, Tampa, FL, USA11 USF Health Morsani College of Medicine, Tampa, FL, USA11 USF Health Morsani College of Medicine, Tampa, FL, USA3 Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA1 Department of Medicine III, University Hospital, LMU Munich, Germany3 Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA8 Department I of Internal Medicine, Medical Faculty and University Hospital, Cologne, University of Cologne, Germany7 Institute for Medical Information Processing, Biometry, and Epidemiology, LMU Munich, Germany9 Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Tumorimmunology, Berlin, Germany10 Department of Internal Medicine 5, Hematology and Oncology, University of Erlangen-Nuremberg, Germany3 Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA1 Department of Medicine III, University Hospital, LMU Munich, Germany6 Department of Hematology, Vall d’Hebron Institute of Oncology (VHIO), University Hospital Vall d’Hebron, Department of Medicine, Universitat Autònoma of Barcelona (UAB), Spain1 Department of Medicine III, University Hospital, LMU Munich, Germany3 Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USAReal-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.http://journals.lww.com/10.1097/HS9.0000000000000907 |
| spellingShingle | Veit Bücklein Ariel Perez Kai Rejeski Gloria Iacoboni Vindi Jurinovic Udo Holtick Olaf Penack Soraya Kharboutli Viktoria Blumenberg Josephine Ackermann Lisa Frölich Grace Johnson Kedar Patel Brian Arciola Rahul Mhaskar Anthony Wood Christian Schmidt Omar Albanyan Philipp Gödel Eva Hoster Lars Bullinger Andreas Mackensen Frederick Locke Michael von Bergwelt Pere Barba Marion Subklewe Michael D. Jain 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 HemaSphere |
| 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 |
| url | http://journals.lww.com/10.1097/HS9.0000000000000907 |
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