Impact of TP53 mutations on survival outcomes in the CAR-T era of large B-cell lymphoma

PurposeTP53 mutations are among the strongest adverse prognostic factors in large B-cell lymphoma (LBCL) treated with chemoimmunotherapy. Whether this unfavorable prognostic impact persists in the era of chimeric antigen receptor (CAR) T-cell therapy remains controversial, largely due to the lack of non–CAR-T comparator cohorts.

We aimed to explore whether the adverse prognostic impact of TP53 mutations differs according to treatment modality, particularly in patients receiving CAR-T therapy versus chemotherapy-based approaches.Patients and methodsWe retrospectively analyzed 195 adult patients with r/r LBCL who underwent Next-Generation Sequencing (NGS). TP53 mutations were identified in 75 patients (38%).

Overall, 151 patients received CD19-directed CAR-T cell therapy, while 44 received non–CAR-T chemotherapy-based treatments. Mutational architecture, including mutation type (missense vs.

disruptive) and protein domain (DNA-binding domain [DBD] vs. non-DBD), was also evaluated within the TP53-mutant cohort.

Patients were stratified into four groups according to TP53 mutation status and treatment modality. Treatment responses were assessed per Lugano 2014 criteria.