Key Points

Multiple myeloma is a plasma cell tumor that affects the bone marrow and may cause a multitude of clinical syndromes

Treat of choice is chemotherapy, however radiation is also used in some cases

The prognosis for patients treated for this condition is favorable

Introduction

• The dogs, cats, humans and many other animals have cells that fight off infection called plasma cells. These cells produce antibodies. If one of the plasma cells in the body becomes cancerous, it produces many other plasma cells and forms a tumor called multiple myeloma (MM). Uniquely, this type of tumor usually produces it own specific type of antibody, which causes a variety of clinical syndromes. Multiple myeloma is a tumor that develops in multiple bone marrow sites (that is why it is called MM).
• MM cells produce excessive immunoglobulin (antibodies) or a component there of called M-component. The M-component can be any class of immunoglobulin or a portion of the molecule called a light-chain (Bence Jones proteins) or heavy chain molecules (Heavy chain disease).
• Multiple myeloma accounts for less than 1% of all malignant tumors in animals and represents 8% of all cancers of the blood cells.
• The excessive secretion of immunoglobulin or infiltration of an organ (usually bones) cause the clinical signs of MM.
• Conditions that are associated with MM
  • Bone lesions: bones that are very active in the production of blood cells are most commonly affected by MM; these include the ends of long bones of the limbs, back bones, ribs, pelvis and skull. About 25 to 66% of patients that have MM have visible bone lesions. This condition may cause a generalized thinning of the bones (diffuse osteopenia) or round punched out lesions. Due to weakening of the bone fractures of the bone(s) may occur.
  • bleeding tendencies are seen in about 33% of dogs affected by MM. M-components can prevent platelets from functioning properly and interfere with clotting factors; about 33% of the dogs will have this problem.
  • hyperviscosity syndrome is a condition in which the blood gets thicker than normal from excessive amounts of immunoglobulin in the blood stream. This can cause neurological signs such as depression seizures, coma and dementia; about 20% of the dogs will have this problem.
  • kidney failure can be caused by high calcium levels, Bence Jones proteins, hyerviscosity syndrome, tumor infiltration into the kidneys, and kidney infections due to poor immune system. About 33 to 50% of cases have this problem.
  • high calcium level in the blood may be caused by the production of a substance that acts like parathyroid hormone. Destruction of the bone may also cause increased calcium to enter into the blood stream (see fig above).
  • immune deficiency with resultant infections may be caused by displacement of normal cells from the bone marrow by the tumor cells (leaving no room for normal blood cell precursors).

• There are no proven causes of MM, however exposure to the agricultural industry, petroleum products and irradiation are risk factors in humans.

Signs

• The average age of dogs affected with MM is 8 to 9 years and German shepherds are more commonly affected. There is no predilection of males over females.
• Clinical signs in decreasing frequency include lethargy/weakness, lameness, bleeding, eye problems (bleeding into eyes, retinal detachment, blindness), increased thirst and urination and neurological signs.
• Many other nonspecific clinical signs may also be present such as vomiting, weight-loss and just not doing right

Diagnosis

• The ultimate diagnosis of MM is based on finding cancer cells in the bone marrow, finding changes in the bones and finding abnormal proteins in the blood (serum) or urine. If there are no visible bony lesions, the diagnosis is based on finding the cancer cells in the bone marrow (see photo right) and the abnormal protein in the blood (serum).

• Tests that are commonly run in patients that are suspected to have MM include:
  • Compete blood count, chemistry profile, urinalysis
  • Examination of the eyes by an ophthalmologist
  • Serum electrophoresis and immunoelectrophoresis (note that nonsecretory MM can exists and this test may be negative)
  • Testing of the urine for Bence Jones proteins
  • Bone marrow biopsy (normal to have less than 5% plasma cells)
  • X-rays of the bones (see radiograph to the right showing multiple holes in the bone due to the cancer eating the bone).

Treatment

• Treatment for MM is used against the tumor itself and the secondary side effects of the tumor.
• Chemotherapy never eradicates the entire tumor, but reduces the tumor burden significantly so that the patient feels well again.
• Chemotherapy agents
  • Melphalan – alkylating agent is an oral medication that must be given daily to the patient
  • Prednisone – a steroid increases the efficacy of melphalan and is typically discontinued after 2 months of treatment
  • Cyclophosphamide – an alkylating agent can be used in place of melphalan or in combination with melphalan. Some oncologists will use this agent only in cases that have high calcium levels in the blood or if the tumor is widespread
  • Chlorambucil – an alkylating agent can be used to treat MM
• A positive response to chemotherapy includes resolution of clinical signs (may take 3 to 4 weeks to see improvement), improvement of the bony lesions (based on radiographs) and reduction of the immunoglobulins in the blood and Bence Jones proteins in the urine (seen 3 to 6 weeks after induction of treatment).
• Radiation can be used to treat isolated plasma cell tumors
• Fractures of the bone can be repaired

Prognosis

• In a study of 60 dogs treated for MM, 43% had a complete remission, 49% had partial remission, and 8% did not respond to treatment at all.
• The presence of high calcium levels in the blood, Bence Jones proteins in the urine and extensive destruction of the bones are warning signs that chemotherapy may not be very effective.
• The median survival in dogs with MM treated with chemotherapy is 540 days.
• Cats tend to not respond as well as dogs.

References

1. Matus RE, Leifer CE, MacEwen EG Hurvitz AI. Prognostic factors for multiple myeloma in the dog. J Am Vet Med Assoc 1986;188:1288-1291.
2. Fox L, Alter S, Cronin K et al. Feline extramedullary plasmacytoma/multiple myeloma: Preliminary results of a VCOG retrospective study. Proc 19th Annu Vet Canc Soc, 1999, P 42.
3. Vail D. Multiple myeloma. In Withrow SJ, MacEwen EG, Small Animal Clinical Oncology, 3rd ed, Philadelphia, WB Saunders, 2001, pp 626-638.
4. Weber NA, Tebeau CS. An Unusual Presentation of Multiple Myeloma in two cats. J Am Anim Hosp Assoc 1998;34:477-483.
5. Vail D, Thamm DH. Pearls of Veterinary Practice. J Am Anim Hosp Assoc 2005;41:209-214.
6. Hendrix DVH, Gelatt KN, Smith PJ, et al. Ophthalmic disease as the presenting complaint in five dogs with multiple myeloma. J Am Anim Hosp Assoc 1998;34:121–128.