Outcomes of the treatment after anti‐cd19 car‐t therapy failure in patients with aggressive b‐cell lymphoma—analysis of data from the czech republic

Introduction: In patients with aggressive B-cell lymphomas (BCL), the long-term progression-free survival (PFS) after anti-CD19 CAR-T therapy is around 30-40%. The prognosis of patients with progression/relapse after this therapy is poor. There are currently limited data on treatment approaches to improve the prognosis of this group of patients (p) and optimal management is not yet defined. Based on the published data, it seems that some of the new drugs being tested in clinical trials (polatuzumab vedotin, bispecific antibodies, lenalidomide, tafasitamab, selinexor, loncastuximab tesirine) could be used as a "bridge" to allogeneic transplantation, which remains a potentially curative treatment option for some of these patients. Methods: We analyzed patients with aggressive BCL (diffuse large B-cell lymphoma /DLBCL/ – 64p, transformed DLBCL – 19p, high-grade BCL – 12p and primary mediastinal large BCL – 11p) who were treated with anti-CD19 CAR-T cells (tisagenlecleucel 79p and axicabtagene ciloleucel 27p) between Dec 2019 and Dec 2022. This is a multicentre retrospective analysis from 5 university hematological centres, where the patients were referred for CAR-T therapy after ≥ 2 lines of treatment failure from the Czech Republic and Slovakia. We focused on the group of patients who did not respond to this treatment. Results: 106p were treated with anti-CD19 CAR-T therapy. The median follow-up (FU) was 16.4 months. The median PFS and overall survival (OS) were 4.3 and 26.4 months. The overall response rate (ORR) was observed in 63p (60%) with 52% complete response (CR). We further analyzed subsequent therapy in a subgroup of 60p who did not respond to CAR-T treatment (progression in 37p/stable disease in 6p) or had relapse (9p) or progression (8p) after initial response (CR/partial remission). The median FU for failed patients was 9.5 months. Overall, 42p in our cohort received therapy; 18p rapidly progressed and were not treated. 4p were treated with radiotherapy (2p achieved CR) and 38p with systemic therapy (glucocorticoids – 6p, lenalidomide+-rituximab – 6p, chemotherapy+-rituximab – 16p, polatuzumab+bendamustine and rituximab – 6p, CAR-T reinfusion – 2p, other 2p). The ORR after systemic therapy was observed in 17% of patients. Patients who were not treated had more likely massive involvement > 5cm at the time of apheresis (p = 0.02). Of the 60p with CAR-T treatment failure, 39p (65%) died. Median OS for CAR-T therapy failed patients (n=60) was 3.1 months from diagnosis of progression/relapse after CAR-T treatment (6-month and 1-year OS 34.9% and 26%). The median OS were 4.7 for treated and 0.2 months for untreated patients from diagnosis of progression/relapse after CAR-T. The research was funded by: This work was supported by grant AZV NU21-03-00411 from the Ministry of Health of the Czech Republic, by the Cooperatio Program, research area "Oncology and Haematology and by MH CZ – DRO (UHHK, 00179906) Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies Conflicts of interests pertinent to the abstract A. Sýkorová Consultant or advisory role GILEAD, NOVARTIS K. Polgárová Consultant or advisory role GILEAD SCIENCES, NOVARTIS Honoraria: NOVARTIS GILEAD SCIENCES Educational grants: GILEAD SCIENCES F. Folber Consultant or advisory role NOVARTIS, GILEAD SCIENCES K. Steinerová Educational grants: GILEAD SCIENCES D. Belada Honoraria: GILEAD SCIENCES, NOVARTIS Educational grants: GILEAD SCIENCES M. Trněný Consultant or advisory role GILEAD SCIENCES, NOVARTIS Honoraria: GILEAD SCIENCES, NOVARTIS Educational grants: GILEAD SCIENCES R. Pytlík Consultant or advisory role GILEAD SCIENCES, NOVARTIS Educational grants: GILEAD SCIENCES, NOVARTIS