The word “multiple” doesn't mean that myeloma attacks the body in multiple ways. Historically, it refers to the disease often appearing in multiple areas of the bone or bone marrow.
But there really are many different forms of myeloma, and understanding your particular type can help make all those letters and numbers on your lab reports a little less confusing.
It Starts With Plasma Cells
Multiple myeloma is a cancer of plasma cells, a type of white blood cell found primarily in the bone marrow.
Healthy plasma cells make antibodies, also called immunoglobulins, that help protect us from infection. Each antibody is made from heavy chains and light chains.
The five heavy-chain classes are:
IgG, IgA, IgM, IgD and IgE
The two light-chain types are:
Kappa and Lambda
When one abnormal plasma cell begins multiplying uncontrollably, it creates a clone of myeloma cells. Those cells often produce large amounts of one particular antibody—or just part of one.
That's why someone may hear their myeloma described as IgG kappa, IgG lambda, IgA kappa, IgA lambda, or another combination.
IgG Myeloma
IgG is the most common immunoglobulin type associated with multiple myeloma.
A patient may have either IgG kappa or IgG lambda myeloma, depending on which light chain the abnormal plasma cells produce.
IgA Myeloma
IgA myeloma is another relatively common type.
Just like IgG myeloma, it can be associated with either kappa or lambda light chains.
Light-Chain Myeloma
Some myeloma cells don't produce a complete immunoglobulin at all. Instead, they primarily produce abnormal free light chains.
This is known as light-chain multiple myeloma.
The light chains are either kappa or lambda and historically have also been associated with the term Bence Jones proteins, particularly when abnormal light chains are detected in the urine.
Free light chains are especially important because excessive amounts can damage the kidneys.
IgD and IgE Myeloma
IgD myeloma is uncommon, and IgE myeloma is extremely rare.
Because these forms are seen much less frequently, they can sometimes present differently from the more common IgG and IgA forms.
IgM myeloma also exists but is exceptionally rare and must be distinguished from other blood cancers that more commonly produce an IgM monoclonal protein.
Nonsecretory Myeloma
Most people with multiple myeloma have an abnormal protein that doctors can measure in their blood or urine.
A small percentage do not produce easily measurable monoclonal proteins. This is generally referred to as nonsecretory myeloma.
Modern free-light-chain testing has shown that some patients once considered nonsecretory actually produce small amounts of light chains that older testing couldn't detect.
What About Plasmacytoma?
Plasmacytomas are closely related to multiple myeloma, but they aren't simply another subtype of active MM.
A solitary plasmacytoma of bone is a single localized tumor made of abnormal plasma cells in bone without the widespread bone marrow involvement required for a diagnosis of multiple myeloma.
An extramedullary plasmacytoma develops in soft tissue outside the bone marrow, frequently in areas of the upper respiratory tract.
Some people with a solitary plasmacytoma eventually develop multiple myeloma, which is why continued monitoring is important.
Active, Smoldering and MGUS
Another source of confusion is the difference between MGUS, smoldering multiple myeloma and active multiple myeloma.
MGUS involves a small population of abnormal plasma cells or monoclonal protein without the findings required for myeloma.
Smoldering multiple myeloma involves a greater amount of abnormal plasma cells or monoclonal protein but does not meet the criteria for active disease.
Active multiple myeloma is diagnosed when specific myeloma-defining events are present.
Doctors often use the acronym SLiM-CRAB when evaluating this.
CRAB refers to:
C — Calcium elevation
R — Renal (kidney) problems
A — Anemia
B — Bone lesions
The “SLiM” portion adds specific biomarkers that can identify patients at such a high risk of progression that treatment is recommended even before traditional CRAB organ damage develops.
This distinction is important because active myeloma does not always require existing organ damage before treatment begins.
Then There Is the Genetics of Myeloma
Knowing whether someone has IgG kappa or IgA lambda is only one part of understanding their disease.
Doctors also study the genetics of the myeloma cells themselves.
FISH testing looks for specific chromosomal abnormalities within myeloma cells. Certain abnormalities can help doctors understand the biology and risk characteristics of the disease and may influence treatment decisions.
Cytogenetic testing examines chromosomes for abnormalities, although traditional chromosome analysis and FISH provide somewhat different information.
Gene-expression profiling examines patterns of gene activity within myeloma cells. It has been used in research and some specialized settings to help assess disease biology and risk.
These tests don't tell us that someone inherited myeloma. Instead, many of the abnormalities being examined are acquired changes within the cancer cells themselves.
Why Does Your Type Matter?
Multiple myeloma isn't one identical disease shared by every patient.
One person may have IgG kappa myeloma with standard-risk genetic features. Another may have light-chain disease with kidney involvement. Someone else may have IgA lambda myeloma with a high-risk chromosomal abnormality.
They're all living with multiple myeloma, but the biology of their cancers can be very different.
That is one reason myeloma treatment has become increasingly individualized.
Initial treatment today commonly uses combinations of three or four medications from different drug classes, but the exact regimen isn't automatically the same for everyone. Doctors consider factors such as age, overall health, kidney function, transplant eligibility, disease characteristics, genetic risk and previous medical conditions when choosing treatment.
The Most Important Thing to Know
If you've been diagnosed with multiple myeloma, don't be afraid to ask:
What type of myeloma do I have?
Is it kappa or lambda?
What does my FISH testing show?
Do I have any high-risk abnormalities?
How does that information affect my treatment and monitoring?
Multiple myeloma may share one name, but underneath that name are many different biological versions of the disease.
Understanding your myeloma is one of the first steps toward understanding your treatment.
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