Outcomes of CAR T cell therapy in diffuse large B cell lymphoma transformed from follicular lymphoma: a single center retrospective analysis

Introduction Follicular lymphoma (FL) transformation to diffuse large B-cell lymphoma (DLBCL) confers chemotherapy resistance and poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy has transformed treatment of aggressive large B-cell lymphoma, yet outcomes in transformed FL (tFL) remain incompletely characterized. Methods We conducted a single-center retrospective analysis of 30 consecutive patients with tFL who received CAR T-cell therapy. Twenty-six patients (87%) received CD19 CAR T cells; four received alternative products (CD20-targeted, CD19/CD20 dual-targeted, or CD19/CD22 bispecific) based on individualized clinical reasoning. Results Median age was 52 years; 97% had stage 3-4 disease, 40% had bone marrow involvement, and 33% had transformed double-hit lymphoma (DHL). Among 25 patients with available tumor tissue, frequently mutated genes included CREBBP (60%), KMT2D (56%), and TP53 (56%). At median follow-up of 30.5 months, median progression-free survival (PFS) was 11 months and median overall survival (OS) was not reached; 2-year PFS and OS rates were 46.7% and 63.2%, respectively. No patient developed grade ≥3 cytokine release syndrome (CRS) or grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS); however, grade 4 cytopenias and infections were common. In exploratory analyses, ECOG PS >1, bone marrow involvement, DHL, and non-complete remission (non-CR) status at 3 months were associated with inferior OS in univariate analysis. Discussion Multivariable estimates were limited by small event numbers and wide confidence intervals; non-CR status at 3 months and DHL were associated with inferior outcomes in exploratory analyses but should not be regarded as definitively established independent prognostic factors. The high frequency of TP53, CREBBP, and KMT2D mutations underscores the distinct molecular biology of transformed disease; these molecular findings are descriptive and require validation.