Refractory Multiple Myeloma in a West Highland White Terrier: Clinical Presentations and Therapeutic Interventions

Abstract

This report presents the case of a seven-year-old West Highland White Terrier diagnosed with relapsed and refractory multiple myeloma (MM), managed using multiple treatment approaches, including conventional chemotherapy (melphalan, vincristine, doxorubicin, and dexamethasone), radiation therapy (RT), and novel agents such as the selective inhibitor of nuclear export (verdinexor), proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), and tyrosine kinase inhibitors (TKIs; toceranib and sorafenib). Treatment response was monitored using serum globulin concentration and imaging studies. Verdinexor achieved the longest period of stable remission with minimal toxicity post-RT. Bortezomib + dexamethasone was effective in controlling hyperglobulinemia at doses ≥ 1.45 mg/m², although cumulative hematologic and gastrointestinal toxicity limited its prolonged use. Second-line proteasome inhibitors and TKIs demonstrated limited efficacy. Despite initial therapeutic response, the patient's condition deteriorated due to persistent hyperglobulinemia and hyperviscosity syndrome. The absence of advanced supportive options, including plasmapheresis, contributed to a fatal outcome. This case highlights the potential utility of novel therapies such as verdinexor and bortezomib in managing refractory canine MM. Timely intervention, individualized dosing, and supportive care are essential for optimizing treatment outcomes. Further research is required to define effective combinations and integrate advanced care options, including stem cell transplantation and targeted antibody therapies, in veterinary MM.

Keywords: dog; proteasome inhibitor; radiation therapy; tyrosine kinase inhibitor.

Figure 1

Computed tomography (CT) findings in this dog. The mass (arrow) at the level of the third lumbar vertebra (L3) and vertebral osteolysis are identified on the transverse view (pre-contrast) (A). Regions of decreased attenuation are observed in multiple areas of the thoracic and lumbar spine (pre-contrast) (arrows) (B). Osteolytic lesions are noted in the iliac (arrow) (C) and pubic (arrow) (D) regions (post-contrast). Mediastinal lymph nodes (arrows) (E) and liver (arrows) (F) are markedly enlarged (post-contrast).

Figure 2

Magnetic resonance imaging (MRI) findings in this dog. A mass (arrow) at the L3–L4 level is compressing the spinal cord on the T2-weighted, pre-contrast sagittal view.

Figure 3

Electrophoretogram of the dog. A tall and narrow peak in the β-II region.

Figure 4

Cytology of the spleen (A) and liver (B). Round cells are seen predominantly with blue cytoplasm, round nuclei, and perinuclear clear zone (500× magnification, Diff-Quik stain).

Figure 5

Post-contrast CT images of the mass at the L3–L4 vertebral level before (A,B) and after (C,D) radiation therapy. (A,B) Pre-radiation therapy images show a soft tissue attenuation mass (arrows in (A,B)) with dorsal compression of the spinal cord. (C,D) Post-radiation therapy images reveal that the mass (arrows in (C,D)) has transformed to fat attenuation with significant reduction in size and alleviated compression.

Figure 6

Abdominal ultrasonography on day 189 in the dog. A mass measuring approximately 5 cm in diameter is observed in the abdominal cavity, suspected to be an enlarged hepatic lymph node (A). An additional mass is identified at the level of the duodenum (B).

Figure 7

Alopecia, skin eruption, and hyperpigmentation are observed on the pinna, muzzle, neck, axillary region, and forelimbs ((A); arrows), and on the inguinal region and hind limbs ((B); arrow heads).

Figure 8

MRI images of the L3–L4 vertebral level on day 395. (A) T2-weighted image (T2WI), (B) T1-weighted image (T1WI), and (C) post-contrast T1-weighted image. The treated L3 mass (arrows in (A–C)) shows high signal intensity on both T2WI and T1WI, consistent with fat, and has decreased in size. Spinal cord compression is nearly resolved.

Figure 9

Anti-cancer treatment modalities and corresponding serum total protein (TP) and globulin (GLOB) concentrations. M: Melphalan; P: Prednisolone; V: Vincristine; A: Doxorubicin; D: Dexamethasone; RT: Radiation Therapy; Ver: Verdinexor; B: Bortezomib; C: Carfilzomib; I: Ixazomib; S: Sorafenib; Cy: Cyclophosphamide; L: Lomustine; T: Toceranib.