TP53 mutations predict for poor outcomes in patients with newly-diagnosed aggressive B cell lymphomas in the current era.

Genetic subgroups of diffuse large B cell lymphoma (DLBCL) have been identified through comprehensive genomic analysis; however, it is unclear if this can be applied in clinical practice. We assessed whether mutations detected by clinical laboratory mutation analysis (CLMA) were predictive of outcomes in patients with newly-diagnosed DLBCL/high grade B cell lymphoma (HGBL). Patients diagnosed from 2018-2022 whose biopsies underwent CLMA and received R-CHOP or R-EPOCH were analyzed for overall/complete response rate (ORR/CRR) and estimated progression free/overall survival (PFS/OS). CLMA was successfully performed in 117/122 patient biopsies (96%) with a median turnaround time of 17 days. Median length of follow-up was 31.3 months. Of mutations detected in ≥10% of biopsies, only TP53 was associated with both progression and death at 2 years. TP53 mutations were detected in 36% of tumors, and patients with TP53 mutations experienced significantly lower ORR (71% vs 90%, P=0.009), CRR (55% vs 77%, P=0.01), 2 year PFS (57% vs 77%, P=0.006), 2 year OS (70% vs 91%, P=0.001) and median OS post-relapse (6.1 months vs not yet reached, P=0.001) as compared to those without TP53 mutations. Furthermore, patients with TP53 loss of function (LOF) mutations experienced lower rates of 2 year PFS/OS than those with non-LOF mutations, and inferior or near-inferior 2 year PFS if harboring high-risk clinicopathologic features. TP53 mutations identified through CLMA can predict for inferior outcomes in patients with newly-diagnosed DLBCL/HGBL. Results of CLMA can be used in real-time to inform prognosis and/or identify candidates for clinical trials.