Bendamustine induces peripheral lymphodepletion in dogs with relapsed lymphoma.
5 affiliations
- 1Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States.
- 2Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States.
- 3Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
- 4Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
- 5Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Abstract
Background
Chimeric antigen receptor (CAR) T-cell therapy has improved outcomes for many human patients with B-cell lymphoma and provides a rational template for analogous canine patients. To date, the expansion, persistence, and activity of CAR T cells in dogs have been limited. Lymphodepletion supports CAR T-cell engraftment and antitumor activity. In human medical oncology, bendamustine has emerged as a well-tolerated lymphodepleting agent. However, prospective use of bendamustine for dogs with lymphoma has not been characterized.Hypothesis/objectives
To determine the lymphodepleting activity and tolerability of bendamustine in dogs with relapsed lymphoma. Secondary objectives included monitoring serum cytokines and short-term changes in peripheral tumor burden.Animals
Eleven client-owned dogs with relapsed lymphoma.Methods
Luminescent assays were used to assess the direct cytotoxic activity of bendamustine against canine lymphoid cell lines. A prospective rapid dose-escalation pilot trial was undertaken in 11 dogs with relapsed lymphoma to evaluate tolerability while tracking peripheral lymphocyte counts, serum cytokine concentrations, and lymph node measurements.Results
Bendamustine induced concentration-dependent cytotoxicity in all cell lines tested. Two-dose bendamustine regimens up to 90 mg/m2 were generally well tolerated, with no dose-limiting toxicities observed, and resulted in peripheral lymphodepletion (pretreatment median, 880 cells/μL; posttreatment median, 310 cells/μL), an exploratory decrease in circulating interleukin-6 (pretreatment median, 5.32 pg/mL; posttreatment median, 1.33 pg/mL), and a short-term decrease in peripheral nodal burden in 8 of 11 dogs.Conclusions and clinical importance
Bendamustine was generally well tolerated and induced lymphodepletion in our cohort. These findings support further evaluation of bendamustine as a preconditioning agent before autologous canine CAR T-cell infusion.
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BibTeX
@article{lenz2026bendamustine,
title = {{Bendamustine induces peripheral lymphodepletion in dogs with relapsed lymphoma.}},
author = {Jennifer A Lenz and Laurel Upton and Jonathan Ma and Mia M Talone and Brandon Peng and Lang Jiang and Audrey Ghanian and Dillon Didehvar and Ester Yang and Joseph A Fraietta and Matthew J Atherton},
journal = {Journal of veterinary internal medicine},
year = {2026},
month = nov,
doi = {10.1093/jvimsj/aalag283},
url = {https://europepmc.org/article/MED/42969556},
note = {CC BY},
}
RIS
TY - JOUR
TI - Bendamustine induces peripheral lymphodepletion in dogs with relapsed lymphoma.
AU - Jennifer A Lenz
AU - Laurel Upton
AU - Jonathan Ma
AU - Mia M Talone
AU - Brandon Peng
AU - Lang Jiang
AU - Audrey Ghanian
AU - Dillon Didehvar
AU - Ester Yang
AU - Joseph A Fraietta
AU - Matthew J Atherton
PY - 2026
DA - 2026/11/01
JO - Journal of veterinary internal medicine
DO - 10.1093/jvimsj/aalag283
UR - https://europepmc.org/article/MED/42969556
AB - Background Chimeric antigen receptor (CAR) T-cell therapy has improved outcomes for many human patients with B-cell lymphoma and provides a rational template for analogous canine patients. To date, the expansion, persistence, and activity of CAR T cells in dogs have been limited. Lymphodepletion supports CAR T-cell engraftment and antitumor activity. In human medical oncology, bendamustine has emerged as a well-tolerated lymphodepleting agent. However, prospective use of bendamustine for dogs with lymphoma has not been characterized.Hypothesis/objectives To determine the lymphodepleting activity and tolerability of bendamustine in dogs with relapsed lymphoma. Secondary objectives included monitoring serum cytokines and short-term changes in peripheral tumor burden.Animals Eleven client-owned dogs with relapsed lymphoma.Methods Luminescent assays were used to assess the direct cytotoxic activity of bendamustine against canine lymphoid cell lines. A prospective rapid dose-escalation pilot trial was undertaken in 11 dogs with relapsed lymphoma to evaluate tolerability while tracking peripheral lymphocyte counts, serum cytokine concentrations, and lymph node measurements.Results Bendamustine induced concentration-dependent cytotoxicity in all cell lines tested. Two-dose bendamustine regimens up to 90 mg/m2 were generally well tolerated, with no dose-limiting toxicities observed, and resulted in peripheral lymphodepletion (pretreatment median, 880 cells/μL; posttreatment median, 310 cells/μL), an exploratory decrease in circulating interleukin-6 (pretreatment median, 5.32 pg/mL; posttreatment median, 1.33 pg/mL), and a short-term decrease in peripheral nodal burden in 8 of 11 dogs.Conclusions and clinical importance Bendamustine was generally well tolerated and induced lymphodepletion in our cohort. These findings support further evaluation of bendamustine as a preconditioning agent before autologous canine CAR T-cell infusion.
SN - 0891-6640
SN - 1939-1676
ER -