Opportunities and challenges of active immunotherapy in dogs with B-cell lymphoma: a 5-year experience in two veterinary oncology centers

Abstract

Background Pet dogs spontaneously develop lymphoma. An anthracycline-based multidrug chemotherapy regimen represents the treatment cornerstone; however, cure is rarely achieved. We have been treating dogs with B-cell lymphoma with an autologous vaccine (APAVAC®) and CHOP-based chemotherapy since 2011. Methods To better characterize the safety and efficacy of APAVAC®, and to find the best candidates for immunotherapy, we designed a retrospective study on all dogs treated with chemo-immunotherapy to date and compared them with those dogs treated with chemotherapy only. All dogs were completely staged and re-staged at the end of treatment. The primary endpoint was the effectiveness of chemo-immunotherapy, measured as time to progression (TTP), lymphoma-specific survival (LSS), and 1-, 2-, and 3-year survival rates. The secondary objective was safety. Results Three hundred dogs were included: 148 (49.3%) received chemotherapy and 152 (50.7%) chemo-immunotherapy. Overall, the latter survived significantly longer (median LSS, 401 vs 220; P < 0.001). Among dogs with diffuse large B-cell lymphoma, the 1-, 2- and 3-year survival rates were 20, 13 and 8% for chemotherapy, and 51, 19 and 10% for chemo-immunotherapy. The benefit of chemo-immunotherapy was particularly relevant in dogs with concurrent high serum LDH, stage V, substage a disease and not previously treated with steroids (median LSS, 480 vs 85 days; P < 0.001). Among dogs with nodal marginal zone lymphoma, those having at least 3 of the aforementioned characteristics significantly benefited from chemo-immunotherapy (median LSS, 680 vs 160 days, P < 0.001). The 1-, 2- and 3-year survival rates were 30, 16 and 10% for chemotherapy, and 55, 28 and 10% for chemo-immunotherapy. Among dogs with follicular lymphoma, lack of immunotherapy administration was the only variable significantly associated with increased risk of tumor-related death. Chemo-immunotherapy was remarkably well tolerated, with no local or systemic adverse events. Conclusions Overall, the addition of immunotherapy to a traditional CHOP protocol is associated with improved outcome in dogs with B-cell lymphoma, regardless of histotype and evaluated prognostic factors. Moreover, the identikit of the best candidate for immune-therapy was delineated for the most common histotypes. The study also confirms the excellent tolerability of the vaccine. Electronic supplementary material The online version of this article (10.1186/s40425-019-0624-y) contains supplementary material, which is available to authorized users.

Immunotherapeutic Strategies for Canine Lymphoma: Changing the Odds Against Non-Hodgkin Lymphoma

“…Overall, compared to dogs treated with chemotherapy only, dogs receiving the chemo-immunotherapy protocol survived significantly longer, regardless of histotype and evaluated prognostic factors. The study also confirmed the excellent tolerability of the vaccine in dogs diagnosed with B-cell lymphomas ( 90 ). Unfortunately, until now there is no information regarding the chemo-immunotherapy treatment response in T-cell lymphoma dogs.…”

The Genetic and Molecular Basis for Canine Models of Human Leukemia and Lymphoma

“…It is not clear if there is a breed-specific predilection for this disease, but several studies of histologically confirmed cDLBCL indicate Golden retrievers, Labrador retrievers, Bernese mountain dogs and German shepherds are commonly affected breeds (10,30,31). Dogs are typically treated with CHOP, with overall survival times varying between studies, from 300 to 500 days (31)(32)(33). Although a number of clinical trials of anti-CD20 therapy in dogs with B cell lymphoma are in progress, to date clinically efficacious antibody therapy is not available for dogs with BCL.…”

Prognostic Value of PD-L1, PD-1 and CD8A in Canine Diffuse Large B-Cell Lymphoma Detected by RNAscope

“…Diffuse large B-cell lymphoma (DLBCL) is the most frequent histotype in dogs, accounting for 50–60% of all non-Hodgkin lymphomas [ 1 ]. Despite its relative morphological and phenotypical homogeneity, DLBCL encompasses multiple clinical entities in dogs, and only a small number of animals is definitively cured by treatment [ 1 , 2 , 3 , 4 , 5 ].…”