Senior Scientist Zoetis Park City, Utah, United States
Abstract:
Background: B-Cell lymphoma is the most common hematological cancer in dogs. The majority of canine B-cell lymphomas express CD20, making it a relevant therapeutic target.
Hypothesis/
Objectives: The objective of this exploratory study was to evaluate the safety and tolerability of escalating, subcutaneously administered doses of a fully canine anti-CD20 monoclonal antibody (mAb) in dogs with multicentric B-cell lymphoma. Secondary objectives included the documentation of preliminary evidence of anti-tumor efficacy and B-cell depletion.
Animals: Sixteen client-owned dogs with cytologically confirmed, substage a, B-cell lymphoma, naïve and relapsed, stages II-V.
Methods: The study was conducted as an open-label, dose-escalation trial at three veterinary oncology specialty hospitals. Dogs were assigned to treatment groups sequentially using a 3+3 dose escalation model, at 0.5, 1.0, 5.0, and 10.0 mg/kg. Adverse events were monitored according to VCOG-CTCAE v2 guidelines and tumor response was assessed according to VCOG response evaluation criteria for lymphoma in dogs (v1.0). B-cell depletion was measured by flow cytometry.
Results: No hypersensitivity reactions or dose limiting toxicities occurred. An objective response was seen in 43.75 % (7/16) of dogs at any time point; 43.75 % (7/16) had stable disease, and 12.5 % (2/16) had progressive disease. B-cell depletion was observed at all time points in the 5.0 mg/kg and 10.0 mg/kg dose groups.
Conclusions and Clinical Importance: Canine anti-CD20 mAb was generally well-tolerated across four dose levels in dogs with multicentric B-cell lymphoma. Evidence of B-cell depletion and tumor response was demonstrated in most dogs. Further investigation is warranted.
Learning Objectives:
Upon completion, participants will be able to describe current therapies for canine B-cell lymphoma and articulate the need for additional therapies with different mechanisms of action.
Upcon completion, particpants will be able to evaluate the study design and outcomes of a dose escalation study for a canine CD20 monoclonal antibody for B-cell lymphoma.
Upon completion, participants will be able to compare the safety and efficacy data for escalating doses of a canine CD20 monoclonal antibody for B-cell lymphoma.
Upon completion, participants will be able to assess the biologic activity and B-cell depletion documented with varying doses of a canine CD20 monoclonal antibody for B-cell lymphoma.
