TP53 ‐Altered Aggressive Large B‐Cell Lymphoma ( LBCL ) Outcomes by Treatment Modality: A Multicenter Cohort From 14 US Centers

Advances in the treatment of large B‐cell lymphoma (LBCL) have expanded therapeutic options beyond conventional chemoimmunotherapy to include cellular and targeted therapies. There is growing interest in identifying subsets of LBCL that may benefit from these novel approaches based on histopathologic and molecular features. Molecular subclassification has identified an LBCL A53 phenotype characterized by TP53 alterations, a subgroup historically associated with poor outcomes following standard therapy. To better define progression‐free and overall survival outcomes in TP53 ‐altered LBCL in the contemporary treatment era, we conducted a multicenter cohort study evaluating responses to first‐, second‐, and third‐line therapies. Our findings demonstrate that TP53 ‐altered LBCL can be cured with first‐line curative intent chemoimmunotherapy. In the second and third‐line setting, outcomes did not significantly differ between different treatment approaches, though improved PFS was seen with CAR‐T in the second line for double hit patients. This study represents the largest reported cohort of patients with TP53 ‐altered LBCL and provides important insights into treatment outcomes across lines of therapy in the era of novel agents.