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Multiple Myeloma

By Arnold Plotnick, MS, DVM, ACVIM

Chemotherapy can be surprisingly effective for this uncommon cancer in cats.

Introduction

Veterinarians are keenly aware of the bizarre tendency for uncommon illnesses to present themselves in “threes”.  I was caught off guard, however, when Katy’s bloodwork arrived on our printer.

Katy is a 13 year-old female cat belonging to Michael Thomas and Kama Sanguinetti.  She had a mammary adenocarcinoma removed some months before, and I had been monitoring her closely after the surgery, given the malignant nature of these tumors.  Months had gone by with no signs of a recurrence of her mammary cancer, however, Katy’s kidneys gradually began to fail, a common, expected development as cats begin to age.  I had been managing her renal failure, and she seemed to be doing well, however, her owners felt that she was losing more weight.  Being only 7 pounds to begin with, there wasn’t much Katy to spare, and a re-examination was clearly in order.  Chronic renal failure is known to cause weight loss. Was Katy’s kidney failure progressing rapidly, despite our countermeasures?

On physical examination, Katy was bright and alert, her striking yellow-orange coat still nice and shiny.  She basically looked the way she had when I examined her three months earlier, except for the 1 lb. weight loss.  Although one pound doesn’t sound like a lot, this amounted to almost 15% of her body weight.  I suggested we run some tests – a complete blood count, serum chemistry panel, thyroid evaluation, and urinalysis – to get a detailed picture of her current health status. Her owners agreed.

I expected an increase in her kidney parameters.  What I found, however, was a dramatic increase in the level of protein in her bloodstream.  Protein in the bloodstream is divided into two major components: albumin and globulins.  Katy’s globulin level was extremely elevated.  A few other parameters were above or below the normal range, but it was the extreme elevation of the globulin level that was most worrisome.  Although there are several potential causes for elevated globulins, I had recently diagnosed a rare cancer in two other cats with similar bloodwork, and I feared that Katy would complete the triad: I suspected that she had multiple myeloma.

The Globulin Story

The main component of the globulin fraction of the serum is antibodies.  It is not uncommon to see an increased amount of globulins in the bloodstream when a cat has an infectious condition, because the immune system typically responds to infections by increasing production of antibodies. Antibodies are instrumental in helping to fight off the infection.  A slight increase is expected. A massive increase, however, is troublesome.

Globulins are produced by cells of the immune system called plasma cells.  When the immune system is stimulated (for example, by an infection), a variety of different plasma cells will react to the stimulus by producing a wide array of antibodies.  This is reflected in the bloodwork as an elevation in globulins.

Occasionally, and for no discernable reason, one particular plasma cell may become cancerous. That plasma cell will multiply, and multiply, and multiply.  This large population of cancerous plasma cells will produce many identical copies of the particular antibody it is programmed to produce.  This, too, would be reflected in the bloodwork as an elevation in globulins.  How does one determine if the increase in globulins is due to non-specific stimulation of the immune system as if in response to an infection, or if the increase is due to something more ominous, like multiple myeloma?

Proving my Hunch

Serum protein electrophoresis is a test that allows the globulins to be characterized further, by separating them according to their physical properties.  The serum is placed on a gel, and an electrical current is applied.  The globulins migrate across the gel based on their charge and size, and a pattern emerges (Figure 1).  Albumin, a serum protein, appears on the left.  The next five components (the globulins) appear and are labeled alpha 1, alpha 2, beta 1, beta 2, and gamma.  The gamma fraction is where the antibodies are found.  Figure 1 shows a typical, normal pattern.

(Figure 1)

Myeloma figure1

Infectious and/or inflammatory conditions will cause an increase in globulins, and when electrophoresis is performed, the pattern will still look like that in Figure 1, although the gamma peak might be a little bit larger.

If, however, the electrophoresis reveals a very tall, narrow peak in the gamma region (Figure 2), it suggests that multiple copies of an identical antibody have been produced by one particular subset or “clone” of cells.  This narrow peak is called a “monoclonal spike”, meaning one (“mono”) clone (“clonal”) is responsible for the pattern seen.  The list of diseases that can do this is very short, and multiple myeloma is at the top of the list.  This is the pattern that I saw when the laboratory ran the test on Katy’s serum.

(Figure 2)

Myeloma figure 2

Diagnosis of multiple myeloma, however, requires meeting at least two of the following criteria:

  • A monoclonal spike seen on protein electrophoresis
  • Detection of certain proteins, called Bence-Jones proteins, in the urine
  • X-ray evidence of bony lesions
  • Presence of cancerous plasma cells in the bone marrow

We satisfied the first criterion for Katy: the monoclonal spike. We were close to making a definitive diagnosis.

Antibodies are proteins.  A closer look at their structure reveals that antibodies are made up of two large strands or “chains”, and two small chains.  The large strands are called “heavy chains” and the smaller strands are called “light chains”.  Multiple myeloma cells produce large quantities of heavy and light chains, which are then assembled into antibodies.  In normal animals, light chains are not found in urine.  In cats and dogs with multiple myeloma, so many light chains are produced that they may spill over from the bloodstream into the urine.  In the urine, the light chains are known as “Bence-Jones” proteins.  I sent a specimen of Katy’s urine to our diagnostic laboratory, asking them to analyze it for Bence-Jones proteins.  The test came back negative.  This did not mean that she did not have multiple myeloma.  It means that we have to move on to another criterion, and work a little harder to obtain a definitive diagnosis.

Destruction of bone, and the pain associated with it, is a fairly common finding in dogs and humans with multiple myeloma, but not very common in cats.  It is believed that the cancerous cells produce a substance that activates osteoclasts – cells that resorb bone.  On x-rays, the affected bones contain small circular lesions, and are often described as looking as if a “hole-puncher” was used on them.  In dogs, the bones most often involved include the spine, pelvis, ribs, skull, and proximal extremities (the upper part of the legs). In cats, the distal extremities (the lower part of the legs) are reported to be involved as often as the proximal extremities.  Katy’s x-rays were closely evaluated, and were normal.  In order to confirm her diagnosis, we would have to do a more invasive procedure – a bone marrow aspirate.

Multiple myeloma is a cancer of the bone marrow.  As such, evaluation of the bone marrow would be expected to reveal the presence of cancerous plasma cells.  Analysis of the urine for Bence-Jones proteins, and radiographs to look for the presence of bone lysis are usually recommended first, as these are non-invasive procedures and don’t require anesthesia.  In Katie’s case, these tests were negative.  Katy was anesthetized and a bone marrow aspirate and analysis was performed.  The results confirmed the presence of many cancerous plasma cells in her bone marrow.   My suspicions were confirmed.

Treatment

In general, multiple myeloma has been associated with long-term survival when treated with chemotherapy.  “The treatment that we use for dogs also seems to be the most effective in cats,” says Dr. Sue Cotter, an oncologist at the Cummings School of Veterinary Medicine at Tufts University. Prednisone (a glucocorticoid) and melphalan (an alkylating agent), when used in combination, is an effective regimen. “Other drugs might have some efficacy if that combination is not effective” says Dr. Cotter.

I started Katy on prednisolone and melphalan, and she joined Fred and Sophie as the third member of my trio of recently diagnosed multiple myeloma cases.  I hope that Katy will do as well as Bob, a handsome devil of a cat belonging to Doug and Melanie West.  Bob has been receiving prednisone and melphalan for several months, and his multiple myeloma is in complete remission.

Survival time for cats with multiple myeloma is surprisingly good.  For cats that respond to chemotherapy, survival times can be as long as 18 to 24 months, or even longer.  As with all cancers, early diagnosis and treatment is of paramount importance if complete remission is to be achieved.

Common signs of multiple myeloma in cats

  • Decreased appetite
  • Excessive thirst
  • Excessive urination
  • Weight loss
  • Bone pain
  • Bleeding/hemorrhage
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