Where are we with the current state of canine lymphoma treatment? At a recent CVC, Sue Ettinger, DVM, DACVIM (oncology), offered veterinarians some answers to that question.
First, Dr. Ettinger discussed longevity associated with lymphoma treatment as indicated by clinical remission. Often, she says, owners are afraid to initiate cancer treatment because they don’t want to “poison” their dogs. She reiterates to these clients that dogs don’t get sick from chemotherapy—they get sick from lymphoma. While 80% of dogs do have side effects from treatment, treated dogs live significantly longer than dogs without treatment. Lymphoma treatment improves an animal’s survival time and quality of life.
Let’s review the basics
As a refresher, here are a few facts about lymphoma:
> 10% to 25% of tumors in dogs are lymphoma.
> 80% of lymphoma cases in dogs are the multicentric form.
> Most dogs with lymphoma (60-80%) are asymptomatic.
> B-cell versus T-cell lymphoma is an important predictor of prognosis (see “Know your phenotype” below).
Pet owners all want to know what caused their dog’s cancer, Dr. Ettinger says. And the cause is multifactorial. Environmental causes, previous immunosuppression and genetics are all involved, but no direct cause has been established to date.
Here are some characteristics of multicentric lymphoma:
> It’s the predominant cancer in general practice.
> It has a rapid onset.
> It’s most commonly node-based and also involves organs.
> Patients often feel well at the time of diagnosis.
> It’s similar to non-Hodgkin’s lymphoma in people.
Staging tests, in order of importance, are:
> Lymph node aspirate
> Minimum database (complete blood count [CBC], chemistry panel, urinalysis)
> Abdominal ultrasonography
> Chest radiography
> Abdominal radiography
> Bone marrow aspirate
The tests Dr. Ettinger believes are essential before treatment is started are a CBC, a serum chemistry profile, a urinalysis and a lymph node aspirate. Phenotype is important in cases where complete staging is not possible. In her practice, she does not perform a lymph node biopsy in most cases.
Dr. Ettinger finds prescapular and popliteal lymph nodes easiest to aspirate. Her least favorite are submandibular nodes because they’re the most likely to be reactive and are draining the mouth. But if the submandibular nodes are the only ones enlarged, then aspirate them, she says.
Know your phenotype
Phenotype is one of the most important predictors of treatment outcome, as well as whether the dog is sick at time of diagnosis.
Characteristics of B-cell lymphoma:
> It makes up 60% to 80% of lymphoma cases.
> It’s a positive predictor, meaning there’s a higher rate of complete remission and longer remission.
> It’s associated with increased survival time.
> Most B-cell tumors are high-grade.
> It’s common in cocker spaniels and Doberman pinschers.
Characteristics of T-cell lymphoma:
> It makes up 10% to 40% of lymphomas.
> It’s a negative predictor.
> Tumors tend to be hypercalcemic.
> It’s common in boxers.
Golden retrievers are equally represented with B-cell and T-cell lymphoma.
Dr. Ettinger says general practitioners should not do all diagnostics prior to referral, especially in cases where finances are a concern for the owner. She would prefer to save the owner’s money for treatment and help select tests that are prognostic, practical and pertinent to the individual case and client needs. She also does not recommend prednisone before chemotherapy as it makes the chemotherapy less effective and can affect accurate staging as it treats (and kills) the lymphoma cells.
So, is it B or T?
Flow cytometry is the test Dr. Ettinger uses most commonly to determine phenotype once cytology has confirmed a diagnosis of lymphoma, Dr. Ettinger says. This test requires living cells and involves staining those cells with labeled antibodies that bind to proteins expressed on the cell surface. Different types of lymphocytes express different proteins (for example, T cells express the protein CD3 and B cells express CD21). The test reveals how many cells of each type are present.
PCR antigen receptor rearrangement (PARR) is another phenotyping test that allows clinicians to determine the lineage of the cells present and whether they’re monoclonal (indicative of neoplasia) or polyclonal (more consistent with a reactive process). This can be helpful to determine if an enlarged mandibular lymph node is lymphoma or the dog needs a dental.
Dr. Ettinger also uses the Lymphoma Blood Test (LBT) from Avacta Animal Health to monitor patients after they finish chemotherapy. LBT scores can increase less than eight weeks before relapse as determined by lymph node monitoring. In addition, the lowest scores during treatment are also prognostic for survival and time to progression (relapse).
Chemotherapy remains the mainstay of lymphoma treatment, and the Madison, Wisconsin, chemotherapy protocol (CHOP, which includes cyclophosphamide, doxorubicin, vincristine and prednisone, with or without l-asparaginase) is the most successful and very well-tolerated, Dr. Ettinger says. Alternative protocols may be good options for cases with financial or time constraints, and it’s great to be able to offer a range of options for our clients.
While newer treatment products involving monoclonal antibodies have exciting potential, there are some unanswered questions surrounding their use, Dr. Ettinger says. In one commercially available product, the B-cell monoclonal antibody is given in conjunction with chemotherapy, with nine doses administered over eight weeks. The T-cell monoclonal antibody is not adding to overall survival, and Dr. Ettinger is not currently recommending at as part of treatment for dogs with T-cell lymphoma.
In March 2017, a new chemotherapeutic was conditionally licensed for dogs with lymphoma. Tanovea (rabacfosadine—VetDC) is an intravenous chemotherapeutic that can be used as first-line therapy and in dogs at relapse. Initial studies demonstrated reasonable efficacy for dogs that have not been treated with chemotherapy and those that have relapsed. It appears to well-tolerated and Dr. Ettinger is excited to have a new option for studies looking at its use in combination with current drugs.
Lymphoma is one of the most successfully treated cancers in dogs, Dr. Ettinger says, and many patients with lymphoma outlive animals with other diseases such as kidney, heart and liver disease. It’s important to emphasize to owners that dogs treated with chemotherapy live significantly longer than untreated dogs, and chemotherapy is generally well-tolerated in most dogs.