Clinical Rounds: Multiple myeloma in a 9-year-old Labrador

The Clinical Rounds team is from the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, Tennessee.

Clinical rounds coordinator: Jeanne Larson, DVM, DACVIM (oncology)

Medical oncology: Lark Walters, DVM

Clinical pathology: Lisa Viesselman, DVM

Radiology: Marie DeSwarte, DVM, DECVDI, DACVR

Anatomic pathology: Allison Watson, DVM

Radiation oncology: Isabella Pfeiffer, DMV, DECVIM-CA (oncology), DACVR (radiation oncology)

Jeanne Larson, DVM, DACVIM (oncology)Multiple myeloma is a rare cancer in older dogs in which there is neoplastic transformation of an immunoglobulin-producing B-cell (a plasma cell). Multiple myeloma presents as a systemic disease and can affect a variety of organs. In dogs, this cancer commonly infiltrates multiple bone marrow sites, which can result in lytic lesions and cytopenias. Visceral organs may also be affected.

Several paraneoplastic syndromes can be seen with multiple myeloma, including hypercalcemia and hyperviscosity syndrome (HVS). HVS occurs secondary to high concentrations of circulating immunoglobulin and can cause signs such as retinal hemorrhage or detachment, neurologic dysfunction, renal failure and coagulopathies.1

Four diagnostic criteria have been established for canine multiple myeloma, and two of the four criteria must be met for a definitive diagnosis. These include a monoclonal gammopathy, bone marrow plasmacytosis, multifocal lytic bone lesions and Bence Jones proteinuria.

Case presentation

A 9-year-old castrated male Labrador retriever was referred to the University of Tennessee (UT) internal medicine service for further evaluation of a two-week history of urinary and fecal incontinence, progressive weakness, and polyuria with polydipsia. Initial diagnostics performed by his primary veterinarian two days before had revealed an elevated total calcium concentration. Recheck of this parameter upon admission to UT confirmed a hypercalcemia of 16.7 mg/dl (range = 10 to 12 mg/dl). On physical examination, the patient was dehydrated, weak in the hind limbs and dribbling urine. Anal tone was normal. No other physical examination abnormalities were identified.

A complete blood count (CBC), serum chemistry profile, electrolyte panel and urinalysis were performed. In addition to hypercalcemia, the creatinine concentration was mildly elevated at 1.3 mg/dl (range = 0.4 to 1.2 mg/dl), the total protein concentration was elevated at 9.8 g/dl (range = 5.7 to 7.9 g/dl), and the globulin concentration was increased at 5.8 g/dl (range = 2 to 3.2 g/dl). Urine specific gravity was 1.008. An ionized calcium concentration measurement confirmed hypercalcemia with a value of 1.89 mmol/L (range = 1.26 to 1.39 mmol/L).

Thoracic and abdominal radiography and ultrasonography were performed. Radiographs revealed multiple lytic lesions involving the right scapula, left humerus, and thoracic and lumbar vertebrae. Additionally, there were multiple lytic, pathologic rib fractures in various stages of healing. Abdominal ultrasound identified a mildly enlarged right medial iliac lymph node. This lymph node was sampled via ultrasound guidance, but the cytologic results were inconclusive due to low cellularity.  

Supportive care with 0.9% sodium chloride intravenous fluids was instituted overnight to correct dehydration and treat severe hypercalcemia.

Tumor staging and treatment

Because of strong clinical suspicion for multiple myeloma, the patient was transferred to the UT oncology service for further diagnostics. A serum protein electrophoresis was performed, but the results were not conclusive for multiple myeloma because there was a small peak in the gamma region that was approximately 60% as tall as, and only slightly broader than, the albumin peak.

Next, a bone marrow aspirate was performed and there were many well-differentiated plasma cells noted, with large aggregates in several areas. This was interpreted as plasma cell neoplasia. Given the findings of multifocal lytic bone lesions and a bone marrow aspirate positive for plasmacytosis, multiple myeloma was definitively diagnosed.

The dog remained in the intensive care unit for continued fluid therapy. An ionized calcium concentration recheck was reported at 1.69 mmol/L (range = 1.26 to 1.39 mmol/L). Pamidronate was administered to further decrease blood calcium concentrations and to provide analgesia for the lytic bone lesions. Treatment for multiple myeloma was also initiated with intravenous doses of cyclophosphamide and dexamethasone.

The following morning, the patient's ionized calcium concentration was 1.35 mmol/L (range = 1.26 to 1.39 mmol/L). At that time, he had regained strength in his hind limbs and his urinary and fecal incontinence had resolved. He was discharged from UT with oral prednisone, tramadol and gabapentin.

Follow-up

The dog was rechecked the following week, and a complete blood count was performed to evaluate the nadir after cyclophosphamide administration. With no significant abnormalities in the results, it was deemed safe to start daily chemotherapy with melphalan (Alkeran-GlaxoSmithKline) and continued prednisone. A serum chemistry profile and electrolyte profile at that visit revealed a mild hypocalcemia (9.2 mg/dl; range = 10 to 11.9 mg/dl), which was deemed clinically insignificant, and an improvement in the globulin concentration (4.3 g/dl; range = 2 to 3.2 g/dl).

Two weeks later, the patient presented for another recheck. At home, he was reported to have a good energy level and appetite with no evidence of discomfort. He was displaying polyuria and polydipsia (likely secondary to prednisone). A complete blood count showed no significant abnormalities, and a serum chemistry profile and electrolyte panel showed continued mild hypocalcemia (9.3 mg/dl) and further improvement in globulin concentrations (3.9 mg/dl). The melphalan dose was reduced by 50%, and a prednisone taper was started.

At the next recheck, the patient's globulin concentration was normal (2.7 g/dl). Oral pain medications were discontinued entirely. Melphalan was continued at the maintenance dose, and the prednisone taper was continued. Recheck radiographs of the thorax revealed multiple new pathologic rib fractures in various stages of healing, lysis of the fifth sternebral segment and lysis of the right scapula. These findings indicated that despite the globulin concentration being resolved, the patient's myeloma was not in complete remission. He remained comfortable without evidence of bone pain. Melphalan chemotherapy was continued, and rechecks were performed on a monthly basis.

Two months later, a complete blood count and serum chemistry profile identified a mild elevation in globulin concentration (3.4 mg/dl). Recheck thoracic radiographs identified continued healing of the multiple rib fractures, but lysis of the sixth sternebral segment-a new area-was observed. Because of concern regarding multiple myeloma progression, melphalan was increased to the original induction dose.

At the next recheck, the dog was reported to be feeling well at home. Laboratory work revealed persistent mild globulin elevation (3.3 mg/dl). Melphalan was discontinued because of the patient's poor response. Oral cyclophosphamide was prescribed at three doses a week along with oral furosemide. The dosage of prednisone was also increased. Subsequent rechecks showed resolution of the elevation in globulins, indicating a good response to cyclophosphamide.

Two months later, recheck lab work showed a recurrence of hyperglobulinemia (3.8 mg/dl), and oral chlorambucil was prescribed as an alternative chemotherapy agent. One month later, the dog presented to the UT emergency and critical care service with acute onset of vomiting. Abdominal radiography and ultrasonography revealed no specific underlying cause for vomiting but did disclose progressive multifocal lysis of the lumbar spine. Laboratory work also revealed that the dog's globulin concentration had increased to 4.9 mg/dl. Vomiting resolved with supportive care.

Because of further progression of multiple myeloma, the patient was administered doxorubicin as rescue chemotherapy, and oral dexamethasone was substituted for prednisone. The following week, vincristine was administered, and the dog's globulin concentration decreased to 4.3 mg/dl. 

Several weeks later, the dog presented with lethargy and left forelimb lameness that was localized to the elbow. Radiographs of the limb showed no evidence of bone lysis. Pain medications were prescribed, but the patient's discomfort could not be managed. Several days later, the owners elected for humane euthanasia due to poor quality of life. Overall survival time was nine months from diagnosis. Necropsy revealed disseminated bone lysis, including the left humerus.

Reference

1.     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.

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