Oncology Update: Multiple Myeloma
Central Toronto Veterinary Referral Clinic
Kevin Finora DVM, Diplomate ACVIM (Oncology and Small Animal Internal Medicine)
Multiple myeloma (MM) is a round cell or immune system cancer. Multiple myeloma is rare, accounting for less than 1% of all tumours in companion animals. It comprises 8% of hematopoietic tumours. Multiple myeloma is the systemic form of a plasma cell tumour of B-cell lineage. B-cells are responsible within the immune system for producing antibodies. These antibodies appear as the globulin fraction of the total blood protein on a serum biochemical profile. In MM there is systemic clonal expansion of a single plasma cell. Typically this expansion originates in the bone marrow though, rarely, MM can develop as a result of the systemic proliferation of a solitary plasma cell tumour. Multiple myeloma is a disease of middle age with the average age of onset being between 8 and 9 years. There has been one report noting German Shepherds to have a breed disposition. No age association has been reported.
In MM the malignant plasma cells over produce a single type of immunoglobulin, typically IgG or IgA. If IgM is overproduced the disease is called Macroglobulinemia.
The circulation of high globulin levels in MM is responsible for many of the clinical signs associated with this disease. A bleeding diathesis is common and usually manifests as epistaxis or gingival bleeding. Bleeding is the result of thrombocytopathy (platelet dysfunction). Though, high globulin levels can result in platelets becoming coated in protein (globulin), which decreases platelet aggregation ability. Decreased aggregation will cause platelets to lose their ability to initiate hemostasis. When the protein levels in the blood climb, the blood will begin to sludge and hyperviscosity syndrome (HVS) may develop. Signs of HVS include neurological changes (coma, seizure) and ophthalmologic changes (tortuous retinal vessels). The clonal expansion of one antibody will alter the antibody make-up in the body resulting in increased risks of infection in animals, as the immune system is not able to function normally. Concomitant infection is a common feature of MM.
PU/PD is commonly reported. This signs can develop due to two different mechanisms. Firstly, there can be damage to the proximal tubule caused by the presence of light chain proteins in the urine, a common feature of MM. Secondly, MM results in the production of osteoclast activating factor, which leads to hypercalcemia. Hypercalcemia will cause PU/PD by direct toxicity to the renal tubules and by inhibiting the ADH receptors.
In order to make the diagnosis of MM, at least two and preferably three of the following must be present:
- Monoclonal gammopathy noted by serum electrophoresis (bi-clonal gammopathies are sometimes reported)
- The presence of osteolytic, punched out bone lesions
- Bence-Jones proteinuria (urine must be submitted for Bence-Jones proteins, as dip stick analysis will not detect light chain proteinuria)
- Greater than 10% plasma cell infiltration into the bone marrow
Therapy is directed at both reducing the tumour burden and at the clinical signs. For example, emergency exsanguination may be necessary to immediately relieve HVS signs. Oral, slow acting chemotherapy is the hallmark of treatment for dogs with MM. The response is determined by resolution of globulin levels. With treatment 43% of dogs will have a complete response, 49% will have a partial response (decrease of globulins by 50%) and 9% will have no response. Chemotherapy is very successful at resolving clinical signs and causing significant improvements in quality of life. Therapy is chronic and results in prolonged survival times. The median survival time, with treatment, is 540 days, though all dogs will eventually die from the effects of the disease.
Dr. Kevin Finora is a Board Certified Oncologist and Small Animal Internist who is part of the Healthcare Team at the Central Toronto Veterinary Referral Clinic. He is available for referrals and consultations Monday to Thursday (including Monday and Tuesday evenings). Please contact him with any oncology questions or concerns.
Posted by: Michael Goldstein, DVM, Diplomate ACVIM
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