Afucosylated anti-canine CD20 antibody combined with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in dogs with B-cell lymphoma

Abstract

Abstract Background B-cell lymphoma in dogs is a common hematopoietic malignancy, often treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy, but long-term outcomes remain suboptimal. Although CD20 targeting has improved outcomes in humans with non-Hodgkin’s lymphoma, it remains challenging in dogs because of the lack of effective anti-CD20 antibodies. Hypothesis/Objectives We aimed to assess the safety, efficacy, and B-cell depletion kinetics of a novel afucosylated chimeric anti-canine anti-CD20 antibody (4E1-7-B_f) combined with CHOP chemotherapy in dogs with untreated B-cell lymphoma. Animals Thirteen client-owned dogs with high-grade B-cell lymphoma. Methods In this open-label, single-arm, single-center clinical trial, dogs received 4E1-7-B_f with CHOP chemotherapy. Treatment response was assessed using the Veterinary Cooperative Oncology Group criteria, whereas progression-free survival (PFS), overall survival (OS), and adverse events (AEs), and peripheral B-cell kinetics were evaluated. Results All 13 dogs achieved complete response (CR), with a median time to CR of 3 weeks. The median PFS and OS were 340 (95% confidence interval [CI], 87-417) and 458 (95% CI, 196–not estimable) days, respectively. The 1- and 2-year survival rates were 69.2% and 38.9%, respectively. Most AEs were mild to moderate. B-cell depletion lasted for > 200 days in most dogs, with some remaining B-cells deficient for over 300 days. Conclusions and clinical importance The combination of 4E1-7-B_f with CHOP chemotherapy showed promising efficacy and prolonged B-cell depletion. Although direct comparisons cannot be made because of the single-arm design, the results suggest a potential benefit over historical CHOP data. Additional randomized controlled trials are needed to confirm these findings.