Bendamustine induces peripheral lymphodepletion in dogs with relapsed lymphoma

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.

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.

Eleven client-owned dogs with relapsed lymphoma.

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.

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.

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.