Several factors that predict the outcome of large B-cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T-cell therapy can be identified before cell administration.

Autor: Sýkorová A; 4th Department of Internal Medicine - Haematology, University Hospital and Faculty of Medicine, Hradec Králové, Czech Republic., Folber F; Department of Internal Medicine, Haematology and Oncology, Masaryk University Hospital, Brno, Czech Republic., Polgárová K; 1st Department of Medicine-Department of Haematology, Charles University, General University Hospital, Prague, Czech Republic., Móciková H; Department of Haematology, University Hospital Královské Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czech Republic., Ďuraš J; Department of Haemato-oncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic., Steinerová K; Department of Haematology and Oncology, University Hospital, Pilsen, Czech Republic., Obr A; Department of Haemato-Oncology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic., Heindorfer A; Department of Haematology, Hospital Liberec, Liberec, Czech Republic., Ladická M; Clinic of Oncohaematology, Medical Faculty of Comenius University and National Cancer Institute, Bratislava, Slovakia., Lukáčová Ľ; Oncology Clinic, J.A. Reiman Faculty Hospital, Prešov, Slovakia., Čellárová E; Department of Haematology, F.D. Roosevelt University Hospital, Banská Bystrica, Slovakia., Plameňová I; Clinic of Haematology and Transfusion Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia., Belada D; 4th Department of Internal Medicine - Haematology, University Hospital and Faculty of Medicine, Hradec Králové, Czech Republic., Janíková A; Department of Internal Medicine, Haematology and Oncology, Masaryk University Hospital, Brno, Czech Republic., Trněný M; 1st Department of Medicine-Department of Haematology, Charles University, General University Hospital, Prague, Czech Republic., Jančárková T; Department of Haematology, University Hospital Královské Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czech Republic., Procházka V; Department of Haemato-Oncology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic., Vranovský A; Clinic of Oncohaematology, Medical Faculty of Comenius University and National Cancer Institute, Bratislava, Slovakia., Králiková M; Department of Haematology, F.D. Roosevelt University Hospital, Banská Bystrica, Slovakia., Vydra J; Institute of Haematology and Blood Transfusion, Prague, Czech Republic., Smolej L; 4th Department of Internal Medicine - Haematology, University Hospital and Faculty of Medicine, Hradec Králové, Czech Republic., Drgoňa Ľ; Clinic of Oncohaematology, Medical Faculty of Comenius University and National Cancer Institute, Bratislava, Slovakia., Sedmina M; Department of Haematology, F.D. Roosevelt University Hospital, Banská Bystrica, Slovakia., Čermáková E; Department of Medical Biophysics, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic., Pytlík R; Institute of Haematology and Blood Transfusion, Prague, Czech Republic.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2024 Sep; Vol. 13 (17), pp. e70138.
DOI: 10.1002/cam4.70138
Abstrakt: 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).
(© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE