In diffuse large B-cell lymphoma, TP53 disruption has been shown to have a prognostic impact (DLBCL). For a study, researchers sought to examine if TP53 mutations detected by Sanger sequencing, cell of origin (COO) profiles detected by the Lymph2Cx panel on the NanoString platform, and MYC, BCL2 & BCL6 overexpression or re-arrangements detected by immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH) correlated with outcome in DLBCL patients enrolled in the FIL-DLCL04 trial (NCT00499018). About 125 DLBCL patients with tumor blocks were studied. TP53 has mutated in 11/125 (9%) cases; 60/125 patients received high-dose chemoimmunotherapy upfront, similar to the randomization arm; COO was reported in 88 patients: 48 germinal centers B-cell like, 25 activated B-cell like, and 17 unclassified; 26 patients were a double expression in IHC and 11 double hits in FISH.
After a median of 72 months of follow-up, the 5-year failure-free survival (FFS) for TP53 mutant vs wild-type was 24% and 72%, respectively, and the five-year overall survival (OS) was 34% and 83%. For FFS and OS, the adjusted hazard ratio (HR) was 228 [95% CI 089–586, P= 086] and 405 (95% CI 137–1197, P= 0011), respectively. TP53 gene mutation indicated a poor prognosis subgroup in the set of young DLBCL patients, regardless of therapy or other biological indicators.