Specialty Spotlight: Updates in the Treatment of Canine Lymphoma

December 16th, 2024 | Posted in General, Medical Articles

Updates in the Treatment of Canine Lymphoma

Ashleigh Cournoyer, DVM, DACVIM (Oncology)

Lymphoma is the most common form of cancer affecting dogs, originating from the hematopoietic system. Lymphoma is considered a systemic disease; thus, the mainstay of treatment is systemic therapies (chemotherapy, steroids). While traditional cytotoxic agents like doxorubicin, cyclophosphamide, and vincristine have been utilized for decades, there have been recent advancements with the development of newer drugs like Laverdia and Tanovea. These treatments offer alternative options for managing canine lymphoma and expanding the possibility for durable remissions and improved quality of life for our patients.

Laverdia (Verdinexor)

Laverdia is the first veterinary-specific oral chemotherapeutic that offers a novel approach through its action as a selective nuclear export inhibitor (SINE inhibitor). By inhibiting the export of certain proteins that are overexpressed in hematologic malignancies and are important for cell survival and proliferation, Laverdia prevents cancer cells from reproducing effectively. SINE compounds have demonstrated efficacy against Non-Hodgkin’s lymphoma in humans and are currently being evaluated in clinical trials for other hematologic malignancies in people.

One of Laverdia’s significant advantages is its oral administration, providing a more convenient treatment option compared to traditional high-dose injectable chemotherapeutics administered in-hospital. A phase II clinical trial of dogs with either treatment-naive or relapsed B or T-cell lymphoma treated with single-agent Laverdia had an objective response rate (ORR) of 37%. Most notably, dogs with T-cell lymphoma had an ORR of 71%.

The goal of Laverdia treatment in dogs with lymphoma is generally not to induce a durable remission but rather to provide an improved quality of life and maintain stable disease for a slightly longer period of time than that achieved with steroids alone. Laverdia is well-tolerated, with manageable side effects. Common adverse effects can include mild to moderate anorexia, elevated liver enzymes, and rarely low white blood cell counts (though these are typically less severe than what is often seen with traditional chemotherapy.)

A recent individual case report and small case series have suggested promising efficacy of Laverdia against epitheliotropic cutaneous lymphoma. However, larger prospective studies would ultimately be required to confirm this finding.

Tanovea-CA1 (Rabacfosadine)

Tanovea is an injectable chemotherapy drug approved by the U.S. Food and Drug Administration (FDA) specifically for the treatment of canine lymphoma. This novel treatment is a prodrug that releases a cytotoxic agent capable of disrupting DNA synthesis and cell division, targeting rapidly dividing cancer cells. One of Tanovea’s key benefits is its unique mechanism of action that differentiates it from traditional chemotherapy drugs. It provides an alternative for dogs that do not respond well to standard therapies such as CHOP. It can also be used as a single-agent protocol for owners who are unable to pursue more frequent weekly chemotherapy protocols, as Tanovea is administered once every 3 weeks. Tanovea-CA1 was initially conditionally approved in 2016 and fully approved in 2021.

A phase I/II trial of dogs with treatment-naive or relapsed B or T-cell lymphoma treated with Tanovea had an ORR of 79% (100% in treatment-naive setting, 62% for relapsed patients). Tanovea has also been utilized in an alternating protocol with Doxorubicin, with a similar progression-free survival time to those reported with standard-of-care CHOP chemotherapy but overall lower response rates. Tanovea has also demonstrated efficacy against epitheliotropic cutaneous lymphoma and multiple myeloma.

Adverse effects associated with Tanovea can include lethargy, low white blood cell counts, elevated liver enzymes, gastrointestinal upset, dermatologic toxicity, and rarely pulmonary fibrosis.

– Ashleigh Cournoyer, DVM, DACVIM (Oncology)

References: 

1. Muqbil I, Aboukameel A, Elloul S, et al. Anti-tumor activity of selective inhibitor of nuclear export (SINE) compounds, is enhanced in non-Hodgkin lymphoma through combination with mTOR inhibitor and dexamethasone. Cancer Lett. 2016;383(2):309-317. doi:10.1016/j.canlet.2016.09.016
2. Sadowski, A. R., Gardner, H. L., Borgatti, A., Wilson, H., Vail, D. M., Lachowicz, J., Manley, C., Turner, A., Klein, M. K., Waite, A., Sahora, A., & London, C. A. (2018). Phase II study of the oral selective inhibitor of nuclear export (SINE) KPT-335 (verdinexor) in dogs with lymphoma. BMC veterinary research, 14(1), 250. https://doi.org/10.1186/s12917-018-1587-9
3. London CA, Bernabe LF, Barnard S, et al. Preclinical evaluation of the novel, orally bioavailable Selective Inhibitor of Nuclear Export (SINE) KPT-335 in spontaneous canine cancer: results of a phase I study. PLoS One. 2014;9(2):e87585. Published 2014 Feb 4. doi:10.1371/journal.pone.0087585
4. Grady JL, Gencher J, Adrianowycz S, Martinez-Romero G. Clinical Remission of Cutaneous Lymphoma in a Dog Treated with Verdinexor. J Am Anim Hosp Assoc. 2024;60(5):223-226. doi:10.5326/JAAHA-MS-7443
5. Vlodaver EM, Keating MK, Bidot WA, Bruyette DS, Rosenkrantz WS. Efficacy of verdinexor for the treatment of naïve canine epitheliotropic cutaneous T-cell lymphoma: An open-label pilot study. Vet Dermatol. Published online July 29, 2024. doi:10.1111/vde.13280
6. Vail DM, Thamm DH, Reiser H, et al. Assessment of GS-9219 in a pet dog model of non-Hodgkin’s lymphoma. Clin Cancer Res. 2009;15(10):3503-3510. doi:10.1158/1078-0432.CCR-08-3113
7. Thamm DH, Vail DM, Kurzman ID, et al. GS-9219/VDC-1101–a prodrug of the acyclic nucleotide PMEG has antitumor activity in spontaneous canine multiple myeloma. BMC Vet Res. 2014;10:30. Published 2014 Jan 25. doi:10.1186/1746-6148-10-30
8. Morges MA, Burton JH, Saba CF, Vail DM, Burgess KE, Thamm DH. Phase II evaluation of VDC-1101 in canine cutaneous T-cell lymphoma. J Vet Intern Med. 2014;28(5):1569-1574. doi:10.1111/jvim.12429
9. Saba CF, Fan TM, Phillips BS, Wright ZM, Thamm DH. Alternating rabacfosadine and doxorubicin for treatment of naïve canine lymphoma. Vet Comp Oncol. 2024;22(2):278-283. doi:10.1111/vco.12975