AIM: The aim of this study was to analyse the outcomes of patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CAR-Tx), with a focus on outcomes after CAR T-cell failure, and to define the risk factors for rapid progression and further treatment. METHODS: We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd-line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022. RESULTS: The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression-free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty-three patients (59%) were refractory or relapsed after CAR-Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow-up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR-Tx. Risk factors for not receiving further therapy after CAR-Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS-2 (from R/P after CAR-Tx) was 6.7 months (6-month 57.9%) for treated patients and 0.4 months (6-month 4.2%) for untreated patients (p < 0.001). The median PFS-2 (from R/P after CAR-Tx) was 3.2 months (6-month 28.5%) for treated patients. The risk factors for a shorter PFS-2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS-2 for treated patients. CONCLUSION: Our findings allow better stratification of CAR-Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement).

1st Department of Medicine Department of Haematology Charles University General University Hospital Prague Czech Republic

4th Department of Internal Medicine Haematology University Hospital and Faculty of Medicine Hradec Králové Czech Republic

Clinic of Haematology and Transfusion Medicine Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

Clinic of Oncohaematology Medical Faculty of Comenius University and National Cancer Institute Bratislava Slovakia

Department of Haemato Oncology Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic

Department of Haemato oncology University Hospital Ostrava and Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Haematology and Oncology University Hospital Pilsen Czech Republic

Department of Haematology F D Roosevelt University Hospital Banská Bystrica Slovakia

Department of Haematology Hospital Liberec Liberec Czech Republic

Department of Haematology University Hospital Královské Vinohrady and 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Internal Medicine Haematology and Oncology Masaryk University Hospital Brno Czech Republic

Department of Medical Biophysics Faculty of Medicine in Hradec Kralove Charles University Hradec Kralove Czech Republic

Institute of Haematology and Blood Transfusion Prague Czech Republic

Oncology Clinic J A Reiman Faculty Hospital Prešov Slovakia

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