Prognostic impact of TP53 mutation in newly diagnosed diffuse large B-cell lymphoma patients treated in the FIL-DLCL04 trial

The prognostic role of TP53 disruption has been established in diffuse large B-cell lymphoma (DLBCL). Aim of this analysis was to correlate TP53 mutations by Sanger sequencing, cell of origin (COO) profile by Lymph2Cx panel on the NanoString platform and MYC, BCL2 and BCL6 overexpression or re-arrangements by immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH), with outcome in DLBCL patients enrolled into the FIL-DLCL04 trial (NCT00499018). One hundred and twenty-five DLBCL patients with tumour block available were analyzed. TP53 was mutated in 11/125 (9%) cases; 60/125 patients received high-dose chemoimmunotherapy up-front, as for the randomization arm; COO was reported in 88 patients: 48 germinal centre B-cell like, 25 activated B-cell like and 17 unclassified; 26 patients were double expressors in IHC and 11 double hit in FISH. After a median follow-up of 72 months, five-year failure-free survival (FFS) for TP53 mutated versus wild-type was 24% and 72%, and five-year overall survival (OS) was 34% and 83%, respectively. Adjusted hazard ratio (HR) was 2 center dot 28 [95% confidence interval (CI) 0 center dot 89-5 center dot 86, p = 0 center dot 086] and 4 center dot 05 (95% CI 1 center dot 37-11 center dot 97, p = 0 center dot 011) for FFS and OS, respectively. In this series of young DLBCL patients, TP53 gene mutation identified a poor prognosis subgroup, regardless of treatment and other biological markers.

Automated summary

TP53 disruption has been established as a poor prognostic factor in DLBCL patients, regardless of treatment and other biological markers. The mutation in TP53 gene indicates a subgroup with unfavorable outcome in young DLBCL patients.