Prognostic impact of TP53 mutations in diffuse large B-cell lymphoma

To evaluate the prognostic value of TP53 mutations in patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively analyzed the clinical data and gene sequencing results of 253 newly diagnosed DLBCL. Survival and correlation analyses were performed. We further revealed significant prognostic heterogeneity among different TP53 hotspot mutations, with mutations at codons G245, R175, R273, and R282 indicating a poorer prognosis. Within the DBD, mutations in exons 5, 7, and 8 were associated with poorer PFS, while mutations in exons 5, 6, and 8 were linked to poorer OS. Additionally, mutations in the Loop-L2, Loop-L3, and LSH motifs within the DBD were all significantly associated with unfavorable PFS and OS. Notably, in the cohort treated with R-CHOP plus novel agents (R-CHOP + X), there were no significant differences in response rates or survival between TP53-mutated and TP53 wild-type patients, suggesting this combination may overcome the adverse prognosis associated with TP53 mutations.TP53 mutation is a crucial adverse prognostic factor in DLBCL. Given the significant prognostic heterogeneity among different TP53 hotspot mutations, a more refined risk stratification based on the TP53 mutational profile is warranted in clinical practice. For patients with high-risk mutations, combining R-CHOP with targeted therapies and exploring novel combination strategies targeting specific pathways are recommended. In contrast, standard R-CHOP may remain an appropriate option for patients with low-risk mutations. Future prospective trials are needed to validate the efficacy of R-CHOP combined with targeted agents in TP53-mutated DLBCL to optimize treatment strategies and improve patient outcomes. TP53mutations occur in approximately one-third of diffuse large B-cell lymphoma (DLBCL) patients. Missense mutations in the DNA-binding domain are the most common type of TP53alterations. Specific hotspot mutations (R273, R248, R175) are associated with inferior prognosis. TP53 mutation status provides independent prognostic information beyond the International Prognostic Index. Combined analysis of TP53 mutation and protein expression improves risk stratification.