Advances and Treatment of Diffuse Large B Cell Lymphoma in Humans: Potential Applications in Dogs

Presentation Description / Summary: 
Presentation Description / Summary: Diffuse Large B Cell Lymphoma (DLBCL) is the most common form of lymphoma in humans and dogs. While R-CHOP has been the standard of care therapy in humans for many years, the lack of appropriate monoclonal antibodies to add the "R" (Rituximab) to our protocol makes CHOP the current standard of care therapy for dogs. The past 5 years have seen notable advances in DLBCL therapy for human patients. A better understanding of the complex molecular subtypes of DLBCL provides a window of opportunity to employ targeted therapies. Comprehensive genome profiling in human DLBCL identifies distinct subtypes of this disease, with potentially actionable mutations discovered. Similar studies are being undertaken for canine lymphomas.  Most of the progress in human disease has been through the application of advanced immunotherapy strategies.  Human treatment advances involve refinements in bone marrow transplantation, CAR-T therapy, bispecific T-Cell engagers, antibody-drug or antibody-toxin conjugates and other immune-based approaches. We are making inroads into these strategies for our canine patients. However, the timeline for clinical accessibility of these advanced immunotherapeutics is not clear, and the costs, as noted in human oncology, may prove excessive for current veterinary practice.  This presentation will focus on the rationale for including new strategies with novel agents that are practical for translation into canine treatment. First- and second-generation small molecular inhibitor drugs such as ibrutinib, bortezomib, lenolidomide, venetoclax, sirolimus, vorinostat and others are being explored for clinical veterinary practice. Incorporating established drugs such as verdinexor and other commercially available oncology drugs into DLBCL protocols can be considered. While speculative, this lecture aims to revisit opportunities for incremental improvement in DLBCL treatment for dogs going forward.