Concurrent use of rabacfosadine and L‐asparaginase for relapsed or refractory multicentric lymphoma in dogs

Abstract

Background Rabacfosadine (RAB), a novel antineoplastic agent conditionally licensed for the treatment of lymphoma in dogs, is efficacious in both naïve and previously treated dogs. Its use in combination with L‐asparaginase (L‐ASP) has not been studied. Hypothesis/Objectives To evaluate the safety and efficacy of L‐ASP given concurrently with RAB in dogs with relapsed multicentric lymphoma. Animals Fifty‐two dogs with relapse of lymphoma after treatment with at least 1 doxorubicin‐based chemotherapy protocol. Methods Open‐label, multicenter, prospective single‐arm clinical trial. Dogs were treated with RAB at 1.0 mg/kg IV every 21 days for up to a total of 5 doses. L‐asparaginase was administered at 400 IU/kg SQ concurrently with the first 2 treatments of RAB. Results The overall response rate (ORR) for all dogs was 67%, with 19 dogs (41%) achieving a complete response (CR). The median progression‐free survival time (MPFS) was 63 days (range 5‐428 days). Dogs experiencing a CR as their best response had an MPFS of 144 days (range 44‐428 days). Adverse events were similar to previous studies evaluating single agent RAB. Failure to achieve a CR and having previously received L‐ASP were negative prognostic factors on multivariate analysis. Conclusions and Clinical Importance Concurrent RAB/L‐ASP appears to be both efficacious and safe for treating relapsed multicentric lymphoma in dogs. Adverse events were most often mild and no unexpected toxicoses were observed.

L-Asparaginase, Doxorubicin, Vincristine, and Prednisolone (LHOP) Chemotherapy as a First-Line Treatment for Dogs with Multicentric Lymphoma

“…Lymphoma cells are often deficient in asparagine synthetase; therefore, they have an obligate requirement for extracellular asparagine to meet their metabolic needs and maintain cell viability [ 4 ]. L-asparaginase depletes systemic asparagine, thereby interfering with protein synthesis and inducing lymphoma cell death [ 4 , 8 , 9 ].…”

Multicenter, randomized, double‐blinded, placebo‐controlled study of rabacfosadine in dogs with lymphoma

“…Rabacfosadine is well tolerated with mostly low grade adverse events (AEs) observed. 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 Unique AEs associated with RAB have included dermatopathies and pulmonary fibrosis. 6 , 8 , 9 , 10 , 11 , 12 , 13 Dermatopathies usually present as focal erythematous, alopecic, and pruritic lesions, most commonly on the dorsum, inguinal region, and ear canal.…”

Rabacfosadine for naïve canine intermediate to large cell lymphoma: Efficacy and adverse event profile across three prospective clinical trials

“…Studies evaluating RAB in both treatment-naive and relapsed or treatment-refractory dogs with lymphoma have reported overall response rates of approximately 50% to 100%, with higher response rates and longer response durations observed in dogs with Bcell lymphoma and those that are less heavily pre-treated. [9][10][11][12] For the most part, RAB has been well tolerated, typically associated with low grade or mild adverse events (AEs) including neutropenia and gastrointestinal (GI) signs. The dermatologic AE associated with RAB often manifests as pruritic otitis externa and/or erythemic skin lesions on the dorsum and in the inguinal areas.…”

“…According to its label, it may be given every 21 days for up to five treatments to dogs with lymphoma of any type. Studies evaluating RAB in both treatment‐naive and relapsed or treatment‐refractory dogs with lymphoma have reported overall response rates of approximately 50% to 100%, with higher response rates and longer response durations observed in dogs with B‐cell lymphoma and those that are less heavily pre‐treated 9‐12 …”