Abstract: Background – Chemoimmunotherapy including an anti-CD20 monoclonal antibody is the standard of care in human diffuse large B cell lymphoma (DLBCL). An increased knowledge of canine DLBCL biology has led to a resurgence in efforts to incorporate novel agents into veterinary chemoimmunotherapy treatment protocols. However, it is unknown whether stratification of patients into treatment regimens based on a molecular profile will predict treatment outcome.
Hypothesis/Objectives – We hypothesized that differentially expressed gene (DEG) signatures in the pre-treatment lymph node aspirates of dogs with DLBCL would directly correlate with clinical response to chemoimmunotherapy treatment.
Animals – Eighteen dogs were enrolled as part of a prospective, non-randomized clinical trial evaluating the use of combination doxorubicin, anti-CD20 monoclonal antibody, and one of three small molecule inhibitors: KPT-9274, TAK-981, or RV1001.
Methods – We evaluated gene expression in RNA extracted from pre-treatment lymph node aspirates using the NanoString nCounter Canine Immuno-Oncology Panel. Samples were compared within each treatment group based on early (< 90 days) or late (>90 days) progression-free survival (PFS). Trends for selected candidate biomarker genes were confirmed using qPCR.
Results – Prognostic DEGs clustered within each treatment arm, including CREBBP, CDKN1A, TLR3, PI3Kδ, AKT3, PTEN, and NRAS. The presence of pathway alterations downstream of the inhibitor received were associated with PFS.
Conclusions and Clinical Importance – Our findings emphasize the transcriptomic heterogeneity of canine DLBCL and provide a blueprint for validation of clinically relevant biomarkers in prospective chemoimmunotherapy studies.
