Prognostic Impact of TP53 Mutations in Diffuse Large B-Cell Lymphoma

Objective: To evaluate the prognostic value of TP53 mutations in patients with diffuse large B-cell lymphoma (DLBCL). Methods: We retrospectively analyzed the clinical data and gene sequencing results of 253 newly diagnosed DLBCL. Survival and correlation analyses were performed. Results: 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-mut and TP53-wt patients, suggesting this combination may overcome the adverse prognosis associated with TP53 mutations. Conclusion: 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.