Multiple myeloma in a 9-year-old Labrador: Medical oncology perspective

Lark Walters, DVMAn important distinction should be made between multiple myeloma and a related cancer-plasmacytoma. Plasmacytomas tend to be solitary tumors that originate in the soft tissues (extramedullary plasmacytoma [EMP]) or bone (solitary osseous plasmacytoma [SOP]). EMPs of the oral cavity and skin are generally considered to be benign and are treated with surgical excision alone. SOPs are localized to one area of bone at diagnosis and are treated with surgery or radiation therapy, but it is important to recognize that progression to multiple myeloma can be seen months later in dogs with an SOP.1 Additionally, there are rare reports of dogs with more aggressive and multifocal cutaneous plasmacytomas, and these tumors are treated similarly to multiple myeloma.1

Dogs with multiple myeloma may present with a variety of clinical signs, ranging from asymptomatic to presentations of epistaxis or other signs of bleeding, polyuria and polydipsia from hypercalcemia or renal failure, lameness and pain due to bone pathology, or sepsis due to immunodeficiency or leukopenia. Bloodwork findings of cytopenias, elevated total protein and globulin concentrations, or hypercalcemia should raise suspicion for multiple myeloma. The presence of multifocal lytic bone lesions on survey radiographs is also strongly indicative of multiple myeloma.

Supportive care and management of specific multiple myeloma-related complications depend greatly on the underlying pathology. The initial treatment for severe hypercalcemia consists of fluid diuresis (ideally with 0.9% sodium chloride, as it contains no calcium). Bisphosphonates may also be used for the treatment of hypercalcemia and bone pain associated with lysis. The bisphosphonate most commonly used at UT is zoledronate, as it is 100 times more potent than pamidronate and has low-cost generic formulations. Mild to moderate hypercalcemia may resolve with treatment of multiple myeloma alone.

Hyperviscosity syndrome may be treated with plasmapheresis, a procedure in which whole blood is collected and centrifuged to separate plasma from red blood cells and then the red blood cells are suspended in a crystalloid fluid and reinfused.2 Clinically significant bleeding disorders may require blood products, and renal failure should be treated with fluid diuresis. Dogs with a neutrophil count less than 1000/µl or with signs of sepsis should be given antibiotics.

Treatment of multiple myeloma consists of the oral alkylating agent melphalan in combination with prednisone. Melphalan is generally administered long-term, while prednisone is tapered after several months. With this protocol, one study reported that 48% of dogs achieved complete remission, 49% achieved partial remission and only 8% did not respond.3

Response to treatment is typically assessed with bloodwork to monitor globulin concentrations. Additionally, bony lysis can be monitored with serial radiographs. Cytopenias, azotemia and hypercalcemia, if present, can be monitored with serial serum chemistry profiles. In addition to monitoring response to treatment, routine monitoring of CBCs is very important for dogs receiving long-term chemotherapy, as melphalan is cumulatively myelosuppressive. Biweekly CBCs are recommended for the first month and then can be decreased to once a month.  

When relapse of multiple myeloma occurs, rescue treatment options include cyclophosphamide, chlorambucil and lomustine. Another reported rescue protocol includes vincristine, doxorubicin and dexamethasone.1 A measurable objective response was seen in one dog treated with toceranib (Palladia-Zoetis).4 Responses are generally of shorter duration with rescue chemotherapy protocols as compared to treatment with melphalan.  

The prognosis for dogs with multiple myeloma is good. With melphalan and prednisone, the median survival time is 12 to 18 months.3 Known negative prognostic factors for dogs with multiple myeloma include hypercalcemia, Bence Jones proteinuria and extensive bony lysis.3

References

Withrow S, Vail D, Page R. Myeloma-related disorders. In: Vail D, ed. Withrow and MacEwen's small animal clinical oncology. 5th ed. St. Louis: Elsevier, 2013.

Lippi I, Perondi F, Ross SJ, et al. Double filtration plasmapheresis in a dog with multiple myeloma and hyperviscosity syndrome. Open Vet J 2015;5(2):108-112.

Matus RE, Leifer CE, MacEwen EG, et al. Prognostic factors for multiple myeloma in the dog. J Am Vet Med Assoc 1986;188(11):1288-1292.

London CA, Hannah AL, Zadovoskaya R, et al. Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res 2003;9(7):2755-2768.