Canine lymphoma is a major clinical burden, accounting for roughly 7 to 24 percent of all cancers in dogs, with T-cell tumors representing 10 to 38 percent of high-grade, multicentric cases. The standard of care for decades has been CHOP chemotherapy, a multi-drug combination of vincristine, cyclophosphamide, doxorubicin, and prednisone. While CHOP achieves an overall response rate of about 96 percent in T-cell lymphoma, dogs respond less well and relapse sooner than their B-cell counterparts, with a median progression-free survival of just 133 days and a median survival time of around 235 days. The T-cell immunophenotype itself is a recognized negative prognostic indicator, making protocol selection a pressing clinical question.

The biological rationale for turning to alkylating agents lies in the mechanics of drug resistance. T-cell lymphomas in both humans and dogs carry more chromosomal aberrations than B-cell neoplasms, suggesting a greater capacity for acquired drug resistance. Overexpression of ATP-binding cassette transporter proteins, which pump drugs such as doxorubicin and vincristine out of tumor cells, has been documented in canine lymphoma. Crucially, alkylating agents are not substrates for these efflux pumps and show no cross-resistance with them, which has driven interest in alkylator-heavy combinations like LOPP, comprising lomustine, vincristine, procarbazine, and prednisone, and MOPP, which substitutes mechlorethamine for lomustine.

Historically, both protocols have reported response rates comparable to CHOP when used as first-line therapy. LOPP has been associated with overall response rates of 94 to 97 percent and complete response rates of 83 to 90 percent, while MOPP has shown a 98 percent overall response rate and a 78 percent complete response rate in earlier reports. Median survival times have ranged from about 9 months for MOPP to 10 to 17 months for LOPP, both figures generally exceeding the roughly 8 months historically attributed to CHOP in T-cell disease. Until now, however, no study had directly compared the two protocols head to head in dogs with T-cell or hypercalcemic lymphoma, leaving the choice largely to clinician experience, practicality, owner preference, and cost.

The new study included dogs with confirmed intermediate to large cell T-cell lymphoma of multicentric distribution, excluding T-zone lymphoma and cases with gastrointestinal or cutaneous involvement because of their distinct prognoses. Thirty-seven dogs received LOPP and 34 received MOPP, each given on a 28-day cycle for up to six cycles. Diagnosis was established through cytology, histopathology, flow cytometry, and polymerase chain reaction for antigen receptor rearrangement, with immunophenotyping completed in every dog. Flow cytometry, performed in nearly 86 percent of cases, revealed that the dominant immunophenotype was CD4-positive CD8-negative, present in 49 of the 71 dogs. More than half of the dogs were hypercalcemic at diagnosis, and among those undergoing thoracic imaging, just over half harbored a cranial mediastinal mass.

The headline results favored LOPP decisively on two of the four key endpoints. Complete response was achieved in 86 percent of LOPP-treated dogs versus 65 percent of MOPP-treated dogs, a statistically significant difference. Median progression-free survival was 208 days under LOPP compared with 102 days under MOPP, also significant, and multivariable analysis confirmed that LOPP reduced the risk of progression or death by more than two-thirds. Overall response rates, at 97 percent versus 91 percent, did not differ significantly, and median overall survival times were statistically indistinguishable at 298 days for LOPP and 231 days for MOPP. The authors suggest that the survival equivalence likely reflects the wide variety of rescue chemotherapies used after relapse and differing decisions about when to discontinue treatment.

Toxicity profiles were broadly similar between the groups, though the details matter for practicing clinicians. Grade III or higher adverse events occurred in 45.9 percent of LOPP-treated dogs versus 20.6 percent of MOPP-treated dogs, driven largely by myelosuppression, which affected 35.1 percent of LOPP patients. Febrile neutropenia was more frequent with LOPP at 8.1 percent compared with 2.9 percent for MOPP, consistent with lomustine’s dose-limiting toxicity being neutropenia. Hospitalization was required in 18.9 percent of LOPP dogs and 11.8 percent of MOPP dogs, and notably, prophylactic antibiotics, given to more than 62 percent of LOPP patients, did not appear to prevent febrile neutropenia. Treatment delays and dose reductions were common in both arms, and the authors caution that the lower-than-historical doses used in this cohort may explain why survival figures fell short of some earlier LOPP reports.

The study also yielded prognostic insights specific to T-cell disease. Dogs with a cranial mediastinal mass and those with the CD4-positive CD8-negative immunophenotype were more likely to achieve complete remission, an intriguing reversal of the mediastinal mass’s usual status as a negative prognostic marker in mixed-immunophenotype lymphoma populations. Achieving any response, and especially a complete response, strongly prolonged progression-free survival, and complete response also extended overall survival on univariate analysis. Stage V disease emerged as an independent negative prognostic factor for progression-free survival in multivariable analysis. Notably, more MOPP-treated dogs had stage V disease, 47 percent versus 22 percent, which the authors acknowledge could partly account for that protocol’s weaker performance, alongside schedule modifications and the possibility of type II error.

Perhaps the most encouraging finding is the existence of a long-surviving subgroup. A quarter of the dogs treated with these alkylator-rich protocols were still alive at 487 days with LOPP and 389 days with MOPP, echoing historical reports of 25 to 35 percent two-year survival with LOPP and a quarter of MOPP-treated dogs alive at 939 days. Such prolonged survival has not been reported with CHOP in T-cell lymphoma, and identifying which dogs belong to this favorable subset is now a priority. The authors conclude that clinicians considering alkylator-rich multi-drug chemotherapy should favor LOPP over MOPP for its higher complete response rate and longer progression-free survival, while stressing that prospective randomized trials are needed to confirm the result. For now, the median outlook for dogs with multicentric T-cell lymphoma remains a guarded 8 to 9 months, but these data sharpen the treatment algorithm and offer a concrete reason for hope in a meaningful fraction of patients.

Subject of Research: Comparison of LOPP and MOPP alkylator-based chemotherapy protocols for first-line treatment of canine multicentric T-cell lymphoma

Article Title: Retrospective comparison of MOPP versus LOPP for first-line treatment of canine multicentric T-cell lymphoma

Article References: Lounsberry, C., Lindley, S. S., Bergman, N., LaRue, M., Haas-Linden, S., & Smith, A. A. (2025). Retrospective comparison of MOPP versus LOPP for first-line treatment of canine multicentric T-cell lymphoma. Veterinary Oncology, 2(1), Article 22. https://doi.org/10.1186/s44356-025-00039-y

Image Credits: AI Generated

DOI: 10.1186/s44356-025-00039-y

Keywords: canine lymphoma, T-cell lymphoma, LOPP, MOPP, chemotherapy, veterinary oncology, lomustine, mechlorethamine, alkylating agents, complete response, progression-free survival, drug resistance