Everybody reading this article has likely had their life touched by cancer, either personally or through a friend, family member or beloved pet. Cancer is something we all want eradicated. While a complete cure may prove unachievable, making the disease more manageable is possible with the new technologies and advancements coming to the field of canine lymphoma. Why the Type Matters Canine lymphomas are a diverse group and among the most commonly diagnosed cancers in dogs. They collectively represent from 7 to 24 percent of all cancers diagnosed in dogs, according to the National Canine Cancer Foundation. More than 30 types of canine lymphoma have been described, and each can vary tremendously in its behavior. Some progress rapidly and are acutely life-threatening without treatment, while others advance slowly and are managed as chronic diseases. Lymphomas may affect any organ in the body, but they most commonly originate in lymph nodes before spreading to organs such as the spleen, liver and bone marrow. Chemotherapy The term lymphoma refers to a type of cancer derived from a white blood cell called a lymphocyte. In general, lymphoma can be divided into two classes, each with its own prognosis. These two classes—B- or T-cell lymphoma—are based on the cell of origin. The Madison Wisconsin Chemotherapy Protocol (CHOP) is a multidrug rotational chemotherapy and the current standard of care in the treatment of canine lymphoma. Remission duration with CHOP therapy depends on which type of lymphoma a dog has. B-cell lymphoma has an average remission of nine or 10 months and T-cell four to five months with CHOP chemotherapy. Current chemotherapy treatment options use drugs brought over from human medicine, with protocols modified for dogs. One chemotherapy drug designed for and labeled for animals—Tanovea-CA1, from VetDC of Fort Collins, Colo.—has received conditional approval from the U.S. Food and Drug Administration. Antibody Therapy Monoclonal antibodies have been used in concert with traditional chemotherapy in human medicine for the last 10 years. They act by assisting the immune system to identify which cells are cancerous. Cancer cells are notorious for tricking the host’s immune system into believing they are part of the host and, thus, need to be left alone. Monoclonal antibodies utilize proteins that the cancer cells express, bind to them and then flag them so the immune system can recognize them more easily as foreign so they can be eliminated. Monoclonal antibody therapy in veterinary medicine will not replace traditional chemotherapy like CHOP, but it will instead be added to the treatment protocol to improve the outcome. David Vail, DVM, MS, Dipl. ACVIM, an oncology professor at the University of Wisconsin School of Veterinary Medicine, believes that monoclonal antibodies specific to canines will become part of the standard of care for lymphoma treatment within five years. Transplantation Bone marrow and stem cell transplant therapy have been used in dogs diagnosed with lymphoma. Bone marrow transplant has been successful in a small number of cases, as it is available as a treatment option at only a few sites in the United States. Some evidence exists that it may be more effective with B-cell lymphoma, according to Brenda Phillips, DVM, Dipl. ACVIM of Veterinary Specialty Hospital in San Diego. The option is expensive for the pet owner. In addition, bone marrow matching for dogs is poorly advanced compared with the human side. Stem cell transplants are easier on the donor than bone marrow transplants. Both treatment options need to advance to the point where they are cost effective and have high cure rates and low numbers of adverse events. Immunotherapy Immunotherapy is a relatively new treatment modality for treating cancer in dogs. Its purpose is to enhance the dog’s natural defenses to fight cancer. Because of this effect, immunotherapy offers potential advantages over traditional cancer therapy, such as chemotherapy. With traditional anticancer therapy, the goal is to directly target and kill cancer cells. Although the response rate may initially be high, the cancer inevitably mutates and acquires the ability to become resistant. With immunotherapy, the treatment is directed at the noncancerous immune system and not the cancer itself. Thus, resistance is less likely to occur and longer lasting responses to treatment are possible. Adoptive T-cell immunotherapy is able to sidestep the long-term side effects of conventional chemotherapeutic protocols. Moreover, the modified T-cells persist in the circulation and help guard against the cancer’s recurrence. It also has the advantage of a positive response possibly lasting a long time. The concept of treating cancer by harnessing an animal’s immune system to recognize and suppress abnormal cells is the basis of immunotherapy. Timothy Stein, DVM, Ph.D., Dipl. ACVIM, of Austin Veterinary Emergency and Specialty said that while more studies are necessary, “the initial studies evaluating adoptive T-cell therapy provide optimism that we may be able to move beyond the current plateau we’ve reached treating canine lymphoma with conventional chemotherapy.” Another novel option for immunotherapy comes from Elias Animal Health of Olathe, Kan. The company’s platform, called the Elias Cancer Immunotherapy (ECI), triggers the immune system to attack and eliminate cancer cells. Each patient’s cancer is unique, and cancer therapy itself must be unique, CEO Tammie Wahaus said. “This proprietary combination approach utilizes pretreatment with a personalized cancer vaccination followed by ex vivo activated patient-derived cancer neoantigen specific effector T-cells that specifically target the patient’s cancer cells, not normal cells,” she said. One downside, Wahaus said, is that “some patients experience side effects similar to those that the body generates when rejecting an infectious disease such as a flu virus, which can be medically managed with anti-inflammatories.” She also said the dual approach is what makes ECI distinct from other cancer immunotherapies. Yet another technology on the horizon is called checkpoint inhibitors, which act as immunological checkpoints, or brakes, to prevent overactivation of the immune system on healthy cells. Tumor cells utilize these checkpoints to escape detection by the immune system. Inhibitor therapies are being used in people diagnosed with melanoma or lung cancer. They are commonly utilized in conjunction with anticancer vaccination to enhance the vaccine’s activity. Checkpoint inhibitors are showing “exciting” preliminary results in people, Wisconsin’s Dr. Vail said, and “have the potential to be game-changing as an adjunct treatment for certain [canine] cancers.” Veterinary Goals The oncologists interviewed for this article agreed that industry and researchers should strive to produce: Better products with better treatment outcomes. Treatment options that are more affordable for pet owners. Treatment options that require fewer client visits. Conclusion The veterinary profession needs to do a better job of defining cancer from a genetic perspective. Transitioning from a blanket treatment approach based on tumor type to a more precise method based on the exact disease a patient has on a genetic level is paramount. Knowing this information would steer oncologists to use one therapy, or a combination, for a lymphoma patient instead of a one-size-fits-all approach. The future of cancer treatment is personalized medicine to allow for a more manageable disease, a good quality of life and not an automatic death sentence. Dr. Meghan E. Burns owns Connect Veterinary Consulting. Her expertise includes marketing, product and business development, key opinion leader management and medical writing.
