Safety and biologic activity of a canine anti-CD20 monoclonal antibody in dogs with diffuse large B-cell lymphoma

J Vet Intern Med. 2024 May-Jun;38(3):1666-1674. doi: 10.1111/jvim.17080. Epub 2024 Apr 25.

Abstract

Background: To explore the safety and utility of combining low dose single-agent doxorubicin with a canine specific anti-CD20 monoclonal antibody (1E4-cIgGB) in client owned dogs with untreated B-cell lymphoma.

Animals: Forty-two client-owned dogs with untreated B-cell lymphoma.

Methods: A prospective, single arm, open label clinical trial of dogs with B-cell lymphoma were enrolled to receive 1E4-cIgGB and doxorubicin in addition to 1 of 3 immunomodulatory regimens. B-cell depletion was monitored by flow cytometry performed on peripheral blood samples at each visit.

Results: Dogs demonstrated a statistically significant depletion in CD21+ B-cells 7 days following the first antibody infusion (median fraction of baseline at 7 days = 0.04, P < .01) that persisted throughout treatment (median fraction of baseline at 21 days = 0.01, P < .01) whereas CD5+ T-cells remained unchanged (median fraction of baseline at 7 days = 1.05, P = .88; median fraction of baselie at 7 days = 0.79, P = .42; Figure 1; Supplemental Table 3). Recovery of B-cells was delayed, with at Day 196, only 6/17 dogs (35%) remaining on the study had CD21+ counts >0.5 of baseline, indicating sustained B cell depletion at 4+ months after the final treatment. 1E4-cIgGB was well tolerated with only 1 dog exhibiting a hypersensitivity event within minutes of the last antibody infusion.

Conclusions: The canine 1E4-cIgGB anti-CD20 monoclonal antibody is apparently safe when administered with doxorubicin and effectively depletes B-cells in dogs with DLBCL.

Keywords: CD20; canine; lymphoma; monoclonal antibody; veterinary.

Publication types

  • Clinical Trial, Veterinary

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / adverse effects
  • Antibodies, Monoclonal* / pharmacology
  • Antibodies, Monoclonal* / therapeutic use
  • Antigens, CD20 / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Dog Diseases* / drug therapy
  • Dog Diseases* / immunology
  • Dogs
  • Doxorubicin* / administration & dosage
  • Doxorubicin* / pharmacology
  • Doxorubicin* / therapeutic use
  • Female
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / immunology
  • Lymphoma, Large B-Cell, Diffuse* / veterinary
  • Male
  • Prospective Studies