Should I treat dogs with T cell lymphoma with a different chemotherapy protocol than for B cell?

T-cell multicentric lymphomas in dogs present a challenge for clinicians. These aggressive malignancies usually have a significantly poorer prognosis compared to B-cell lymphomas, prompting the need for more effective treatment approaches. Chemotherapy protocols that are feature heavily in drugs from a class known as “alkylating agents” in have emerged as a promising strategy in treating this disease.

Alkylating agents, such as cyclophosphamide, lomustine (CCNU), chlorambucil and melphalan, work by inducing DNA damage that prevents cancer cells from replicating. This mechanism is particularly effective against rapidly dividing cells, such as those found in aggressive T-cell lymphomas. In dogs, alkylator-rich protocols like LOPP regimens have demonstrated potential, with some studies indicating that this approach can lead to improved survival times in dogs with T-cell lymphoma. One study of 35 dogs with T cell lymphoma found that dogs treated with the LOPP protocol, consisting of lomustine, vincristine, procarbazine and prednisolone had a median progression-free survival (PFS) of 431 days and a median survival time (MST) of 507 days (1).  This suggests a significant improvement compared to traditional CHOP protocols (cyclophosphamide, doxorubicin, vincristine, prednisolone), with one study reporting a MST of only 235 days for dogs treated with this protocol (2).

However, the story is different in human medicine, particularly for patients with the equivalent of multicentric T cell lymphoma, which goes by the somewhat prosaic name of peripheral T cell lymphoma not otherwise specified (PTCL-NOS).  Just like in dogs, PTCL-NOS is an aggressive and challenging lymphoma subtype with a poor prognosis, and yet the standard of care approach with people with this disease remains CHOP-based regimens.

There are a few reasons why this may be the case.

1. Lack of Superior Efficacy: Despite their potency, alkylator-rich regimens have not consistently shown superior outcomes in PTCL-NOS compared to CHOP- based regimens (3)

2. Toxicity Concerns: Alkylating agents, especially when used in high doses, are associated with significant toxicity, including severe myelosuppression, organ damage, and an increased risk of secondary cancers. Whilst this is a greater concern in human medicine compared with veterinary due to the much higher dose rates employed, this has resulted in caution in their use.

3. Emergence of Targeted Therapies: The development of targeted therapies and immunomodulatory drugs has shifted the focus away from treatment regimens purely based on traditional chemotherapy in people, reducing the need for more toxic alkylating agents.

 While alkylator-rich protocols such as LOPP demonstrate potential for treating T-cell lymphoma in dogs, caution must be exercised when interpreting results from retrospective studies that use historical controls. These studies, while informative, are limited by biases such as differences in patient populations and the lack of randomisation. Without the rigour of well-designed prospective, randomised controlled trials, conclusions drawn from these studies may not fully capture the effectiveness of LOPP compared to other treatments like CHOP. Until such data are available, the choice of protocol remains heavily dependent on the clinician's experience and judgment.

1.     Morgan E, O'Connell K, Thomson M, Griffin A. Canine T cell lymphoma treated with lomustine, vincristine, procarbazine, and prednisolone chemotherapy in 35 dogs. Vet Comp Oncol. 2018 Dec;16(4):622-629.

2.     Rebhun RB, Kent MS, Borrofka SA, Frazier S, Skorupski K, Rodriguez CO. CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma. Vet Comp Oncol. 2011 Mar;9(1):38-44. 

3.     Dreger, P., Corradini, P., Kimby, E., Kolstad, A., André, M., & Corradini, P. (2012). Conditioning and allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma: A consensus paper by the European Society for Blood and Marrow Transplantation (EBMT) and the European Society for Medical Oncology (ESMO). Bone Marrow Transplantation, 47(3), 309-317.