2026-04-17T05:28:26Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/101052025-05-03T03:20:40Zcom_2072_378070com_2072_378040col_2072_378092

urn:hdl:11351/10105 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 Perez, Ariel Jurinovic, Vindi Holtick, Udo Rejeski, Kai Bücklein, Veit IACOBONI, GLORIA Cèl·lules B - Tumors - Immunoteràpia Avaluació de resultats (Assistència sanitària) DISEASES::Hemic and Lymphatic Diseases::Lymphatic Diseases::Lymphoproliferative Disorders::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, Adoptive ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades linfáticas::trastornos linfoproliferativos::linfoma::linfoma no Hodgkin::linfoma de células B Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunización::inmunización pasiva::transferencia adoptiva::inmunoterapia adoptiva TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento B-cell lymphoma; Tumor burden; Systemic inflammation Linfoma de células B; Carga tumoral; Inflamación sistémica Limfoma de cèl·lules B; Càrrega tumoral; Inflamació sistèmica 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. This work was supported by a Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) research grant provided within the Sonderforschungbereich SFB-TRR 388/1 2021 – 452881907, and DFG research grant 451580403 (to MS). The work was further supported by the Bavarian Elite Graduate Training Network (to MS), the Wilhelm-Sander Stiftung (to MS, project no. 2018.087.1), the Else-Kröner-Fresenius Stiftung (to MS), the Bavarian Center for Cancer Research (BZKF), and NCI Cancer Center Support Grant P30 CA076292. VLB, KR, and VB were funded by the Else-Kröner Forschungskolleg (EKFK) within the Munich Clinician Scientist Program (MCSP). 2023-08-21T09:52:24Z 2023-08-21T09:52:24Z 2023-07-11 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion HemaSphere;7(8) https://doi.org/10.1097/HS9.0000000000000907 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Wolters Kluwer Health Scientia