Rabacfosadine

Dogs with lymphoma that fail cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (CHOP) before completion of their protocol are commonly thought to have poor long‐term outcome, but no previous studies have evaluated the effect of early relapse on progression‐free interval (PFI) or overall survival time (OST) for patients undergoing rescue chemotherapy.

Correlate rescue treatment outcomes in dogs with multicentric lymphoma with outcomes after 1st‐line CHOP chemotherapy.

Data were collected from 6 previous retrospective or prospective studies in 187 dogs with multicentric lymphoma that received 1st‐line CHOP chemotherapy and then received either lomustine (CCNU), L‐asparaginase and prednisone (LAP), or rabacfosadine (RAB, Tanovea), with or without prednisone or L‐asparaginase.

The PFI after initiation of CHOP chemotherapy was significantly associated with response rate postprogression, PFI, and postrescue survival time (ST) for both rescue protocols. Immunophenotype (B‐ vs T‐cell) was not significantly associated with response, PFI or OST for LAP but was significantly associated with response and PFI for RAB.

Dogs that experience short PFI during or after 1st‐line CHOP chemotherapy had lower response rates to rescue treatment, with shorter PFI and ST. Immunophenotype did not significantly affect outcome with LAP but was associated with PFI for RAB.

The current standard of care treatment for canine lymphoma is a multi‐agent, CHOP‐based chemotherapy protocol. Single agent doxorubicin (DOX) is less burdensome; however, multi‐agent chemotherapy protocols are often superior. The recently approved drug rabacfosadine (RAB, Tanovea) provides an attractive option for combination therapy with DOX, as both drugs demonstrate efficacy against lymphoma and possess different mechanisms of action. A previous study evaluating alternating RAB/DOX reported an overall response rate (ORR) of 84%, with a median progression‐free survival time (PFS) of 194 days. The aim of this prospective trial was to evaluate the same protocol in an additional population of dogs. Fifty‐nine dogs with treatment naïve lymphoma were enrolled. RAB (1.0 mg/kg IV) was alternated with DOX (30 mg/m2 IV) every 21 days for up to six total treatments (3 cycles). Response assessment and adverse event (AE) evaluation were performed every 21 days using VCOG criteria. The ORR was 93% (79% CR, 14% PR). The median time to maximal response was 21.5 days; median PFS was 199 days. T cell immunophenotype and lack of treatment response were predictive of inferior outcomes. AEs were mostly gastrointestinal. Six dogs developed presumed or confirmed pulmonary fibrosis; four were grade 5. One dog experienced grade 3 extravasation injury with RAB that resolved with supportive treatment. These data mirror those of the previously reported RAB/DOX study, and support the finding that alternating RAB/DOX is a reasonable treatment option for canine lymphoma.