Introducing CAR T-cell therapy into clinical practice for mantle cell lymphoma: real-world experience from Poland

Mantle cell lymphoma (MCL) accounts for approximately 6% of all non-Hodgkin lymphomas and represents a subtype of B-cell lymphoma associated with poor prognosis.Nearly all patients relapse after first-line chemotherapy [1,2].The introduction of Bruton's tyrosine kinase (BTK) inhibitors has significantly improved outcomes in relapsed/refractory (r/r) MCL, with overall response rates (ORRs) of 68-80% and median progression-free survival (PFS) around 13 months overall and 25 months when used in the second line [3].BTK inhibitors are now the standard of care in the second-line setting.However, prognosis remains poor for patients who are refractory to or relapse after BTK inhibitors, with ORRs for next-line treatments in the range 25-42% and median overall survival (OS) of only 6-10 months [4][5][6].In 2020, based on the results of the ZUMA-2 trial, the first autologous chimeric antigen receptor (CAR) T-cell therapy -brexucabtagene autoleucel (brexu-cel) -was approved for r/r MCL following BTK inhibitor therapy [7].In 2023, Poland introduced national reimbursement for brexu-cel for this indication.Here, we present the first Polish single-center real-world experience with this innovative therapy in r/r MCL. Methods.We retrospectively analyzed data from patients with r/r MCL treated with brexu-cel at our department between November 2023 and June 2025.All patients were enrolled according to the National Health Fund therapeutic program criteria.Following enrollment, leukapheresis was performed and autologous lymphocytes were sent for manufacturing, which lasted approximately 4 weeks.Treatment response was assessed using positron emission tomography-computed tomography (PET-CT) at 1 month and subsequently at 2, 3, 6, 9, and 12 months after infusion.OS was measured from brexu-cel infusion.Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded using American Society of Transplant and Cellular Therapy grading criteria [8].Stata 19.5 BE (StataCorp, College Station, TX, USA) was used for the calculations; the Clopper-Pearson method was applied to determine the 95% confidence intervals (CI).Ethics approval was not required.Results.A total of 18 patients (9 female, 9 male), median age 67 years (range: 52-75) received brexu-cel.All had prior BTK inhibitor exposure.The median number of previous treatment lines was 3 (range: 2-4).Six