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 (LMU Gene Center)
Perez, Ariel (Miami Cancer Institute)
Rejeski, Kai (LMU Gene Center)
Iacoboni, Gloria (Vall d'Hebron Institut d'Oncologia)
Jurinovic, Vindi (Institute for Medical Information Processing, Biometry, and Epidemiology, LMU Munich)
Holtick, Udo (University of Cologne)
Penack, Olaf (Charité-Universitätsmedizin Berlin)
Kharboutli, Soraya (University of Erlangen-Nuremberg)
Blumenberg, Viktoria (LMU Gene Center)
Ackermann, Josephine (LMU Gene Center)
Frölich, Lisa (LMU Gene Center)
Johnson, Grace (USF Health Morsani College of Medicine)
Patel, Kedar (USF Health Morsani College of Medicine)
Arciola, Brian (USF Health Morsani College of Medicine)
Mhaskar, Rahul (USF Health Morsani College of Medicine)
Wood, Anthony (Moffitt Cancer Center (Tampa, Estats Units d'Amèrica))
Schmidt, Christian (LMU Gene Center)
Albanyan, Omar (Moffitt Cancer Center (Tampa, Estats Units d'Amèrica))
Gödel, Philipp (University of Cologne)
Hoster, Eva (LMU Gene Center)
Bullinger, Lars (Charité-Universitätsmedizin Berlin)
Mackensen, Andreas (Friedrich-Alexander-Universität Erlangen-Nürnberg)
Locke, Frederick (Moffitt Cancer Center (Tampa, Estats Units d'Amèrica))
Von Bergwelt, Michael (LMU Gene Center)
Barba, Pere (Universitat Autònoma de Barcelona. Departament de Medicina)
Subklewe, Marion (LMU Gene Center)
Jain, Michael D (Moffitt Cancer Center (Tampa, Estats Units d'Amèrica))

Data:	2023
Resum:	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.
Nota:	Altres ajuts: DFG, German Research Foundation) research grant provided within the Sonderforschungbereich SFB-TRR 388/1 2021 - 452881907; DFG research grant 451580403; Wilhelm-Sander Stiftung (to MS, project no. 2018.087.1)
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	HemaSphere, Vol. 7, Núm. 8 (July 2023) , ISSN 2572-9241

DOI: 10.1097/HS9.0000000000000907
PMID: 37449196

12 p, 5.3 MB

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