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

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).

We aim to evaluate the association of gene alterations and clinical factors with POD12.

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.

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).

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.