PROGNOSTIC FACTORS

The overall response rate for dogs treated with melphalan and prednisone chemotherapy is 92%, with 43.2% of dogs achieving a complete response and 48.6% achieving a partial response. The median survival time of dogs treated with this drug combination is 540 days, which is significantly longer than the survival time of 220 days in dogs treated with prednisone alone.¹ Negative prognostic factors in dogs include hypercalcemia, light chain proteinuria, and extensive lytic bone lesions.¹

Response to therapy and duration of response appear to be more variable in cats. Factors associated with a more aggressive form of the disease and poor prognosis include bone lesions with pathologic fracture, anemia, light chain proteinuria, azotemia, and poor response to treatment.⁵ When treated with melphalan and prednisone chemotherapy, four cats classified as having aggressive disease had a median survival time of five days, whereas the median survival time of five cats with less aggressive disease was 387 days.⁵ Other studies have shown overall less promising results, with a shorter duration of response to treatment and a survival time of six months or less in treated cats.⁴ In cats with multiple myeloma and other related disorders, the degree of plasma cell differentiation is significantly correlated with survival. Cats with well-differentiated tumors (< 15% plasmablasts) have a median survival of 254 days, whereas cats with poorly differentiated tumors (≥ 50% plasmablasts) have a median survival of 14 days.⁶

Clinical response to treatment is assessed based on improvement or resolution of clinical signs and laboratory and imaging abnormalities.

In patients that respond to treatment, improvement in clinical signs and laboratory findings (CBC, serum chemistry profile, and protein electrophoresis) are expected within the first four to eight weeks of treatment.⁵ When assessing serum immunoglobulin, complete remission is defined as normal globulin concentrations or undetectable monoclonal immunoglobulin. Partial remission is defined as a 50% decrease in globulin concentrations.¹ Repeated CBCs to evaluate for resolution of cytopenias as well as serum chemistry profiles to check for resolution of azotemia and hypercalcemia are important.

Repeated assessments of bone marrow aspirates, serum viscosity, and light chain proteinuria are less useful in gauging response to treatment. A bone marrow aspirate is indicated in patients with persistent cytopenias to identify persistent bone marrow involvement vs. myelosuppression secondary to chemotherapy.

Additionally, ultrasonography with or without fine-needle aspiration may be used to evaluate resolution of visceral organ infiltration. Although serial radiographs can be used to assess for improvement of bony changes, radiographic changes may not adequately reflect current disease progression or remission.

NOVEL TREATMENTS FOR MULTIPLE MYELOMA

In people, multiple myeloma remains incurable despite conventional high-dose chemotherapy with stem cell support. Novel treatments for multiple myeloma in people target the interaction between the neoplastic plasma cells and components of the bone marrow microenvironment. Bortezomib, a proteasome inhibitor, has shown therapeutic efficacy in treating both relapsed and previously untreated myeloma patients.^41,42 Bortezomib is a potent inhibitor of myeloma cell growth and survival and also inhibits osteoclast formation and bone resorption, which is important in the development of myeloma bone disease.¹⁸ Thalidomide, an immunomodulatory and antiangiogenic agent, has also shown striking antimyeloma activity as first-line therapy in people or in those with relapsed disease.⁴³

These novel therapeutic agents have been largely unexplored in treating veterinary patients with multiple myeloma. In dogs, oral toceranib phosphate (Palladia—Pfizer Animal Health), a receptor tyrosine kinase inhibitor, has been used to treat two dogs with multiple myeloma.⁴⁴ One dog showed a partial response to treatment; the other dog did not respond to treatment.

SUMMARY

Multiple myeloma is a rare neoplasm in both cats and dogs. Conditions associated with multiple myeloma include hyperviscosity syndrome, bone lesions, hypercalcemia, renal disease, cytopenias, hemorrhagic diathesis, and increased susceptibility to bacterial infection. Multiple myeloma does not appear to have the same biologic behavior in dogs and cats and is best viewed as a heterogeneous disease with a different prognosis, clinical course, and response to therapy both within and between species. Although a good clinical response may be achieved with chemotherapy, eventual relapse of disease is to be expected.

Rachel Sternberg, DVM
Jackie Wypig, DVM DACVIM (oncology)
Department of Veterinary Clinical Medicine
College of Veterinary Medicine
University of Illinois
Urbana, IL 61802

Anne M. Barger, DVM, DACVP
Department of Pathology
College of Veterinary Medicine
University of Illinois
Urbana, IL 61802