Next-generation sequencing for DLBCL patients with early failure after frontline R-CHOP chemo-immunotherapy.

BACKGROUND: Early failure less than 12 months (POD12) of frontline R-CHOP chemo-immunotherapy in very poor outcomes and requires alternative therapy in patients with Diffuse large B-cell lymphoma (DLBCL). AIM: We aim to evaluate the association of gene alterations and clinical factors with POD12. METHODS: The panel included 103 genes that were examined in 26 patients with newly diagnosed DLBCL treated with standard R-CHOP chemo-immunotherapy in the frontline setting therapy using next-generation sequencing. The association of clinical features and gene alterations with early progression was analyzed. RESULTS: POD12 group (n=12) was related to poorer OS with a hazard ratio (HR) of 12.13 (95% confidence interval [CI] 2.34-62.78, p=0.0029). Genes mutated in 96.15% of patients (25/26) were grouped into 11 specific pathways, and the POD12 subtype was mostly characterized by mutations in the epigenetic modulation pathway (33.32% of total variation) and apoptosis/cell cycle/autophagy pathway (20.83% of total variation), whereas the no-POD12 subtype is mostly characterized by mutations in the epigenetic modulation pathway (40.66% of total variation). CD79B mutation frequency was significantly increased in the no-POD12 group compared with the POD12 group (50.00% vs 8.33%, p=0.0357). Not achieving complete response (CR) during interim treatment response was found to be significantly associated with the occurrence of POD12 (p=0.0214). CONCLUSIONS: CD79B wide-type and not achieving CR during interim responses evaluation correlate with POD12. These findings provide a basis for the development of optimal alternative therapies in clinical trials.