What Does M-Protein Spike Mean?

Plasma cells are white blood cells that make antibodies. Normally, thousands of different plasma cell lines each make a slightly different antibody. On a lab test, that variety blurs into a broad hump.

An M protein is different. One plasma cell clone has multiplied and is making millions of copies of a single identical antibody. Because every molecule is the same, they all travel together in the test and pile up in one narrow band. That band is the spike. M stands for monoclonal, meaning one clone.

The spike itself is not a diagnosis. It is a signal that one plasma cell line has taken over more space than it should.

Three blood tests usually appear together, and they answer different questions.

Serum protein electrophoresis, or SPEP. An electric current pulls blood proteins across a gel and sorts them by size and charge. A monoclonal band classically shows up in the gamma region. SPEP is the test that reports the spike as a number, such as 1.2 g/dL.

Immunofixation electrophoresis, or IFE. This one names the protein. It tells you whether the clone is making IgG, IgA, IgM, or IgD, and whether the light chain is kappa or lambda. It is more sensitive than plain electrophoresis and can find small monoclonal light chains the gel misses entirely.

Serum free light chain assay. Light chains are the small arms of an antibody. This test measures unattached kappa and lambda in blood and divides one by the other. The reference range for the kappa to lambda ratio is 0.26 to 1.65. A ratio outside that range suggests one clone is dominating, even when SPEP looks nearly normal.

Some clones make only light chains and no full antibody. Light chains are small enough to pass into urine, where they are called Bence Jones protein. The name comes from an old observation: the protein drops out of solution near 56 degrees Celsius and dissolves again at 100 degrees.

Here is the trap. A routine urine dipstick will not find them. Dipsticks are built to detect albumin, not Bence Jones protein. Someone can have a normal dipstick and heavy light chain excretion at the same time.

The correct test is a 24-hour urine collection with protein electrophoresis and immunofixation. The specimen needs no preservative and can be kept at room temperature.

The National Cancer Institute separates these by the size of the spike and the percentage of plasma cells in the bone marrow.

MGUS, monoclonal gammopathy of undetermined significance. An M protein is present in serum, the bone marrow has fewer than 10 percent plasma cells, and there is none of the organ damage that defines myeloma. Most people with a spike land here.

Smoldering multiple myeloma. Serum monoclonal IgG or IgA of at least 30 g per liter, which is 3 g/dL, or urinary monoclonal protein of at least 500 mg per 24 hours. And, or alternatively, clonal bone marrow plasma cells of 10 to 60 percent. No organ damage yet.

Multiple myeloma. The clone is present and at least one myeloma-defining event has occurred.

Two sets of criteria. The first is remembered as CRAB, for the four organ problems:

• Calcium more than 1 mg/dL above the top of the reference range
• Renal: creatinine above 2 mg/dL, or creatinine clearance under 40 mL/min
• Anemia: hemoglobin below 10.0 g/dL
• Bone: one or more lesions on skeletal x-rays, CT, or PET-CT

The second set was added so treatment need not wait for organ damage. These are the SLiM biomarkers:

• Sixty percent or more clonal plasma cells in the bone marrow
• A serum free light chain ratio of 100 or more, involved over uninvolved
• More than one focal lesion of at least 5 mm on MRI

Any one item from either list moves the diagnosis from smoldering to active myeloma.

The number people want is the yearly risk of progression. NCI reports that in population-based groups, the annual risk of MGUS progressing to a plasma cell or lymphoid cancer runs 0.5 to 1.0 percent. In higher-risk groups it runs from 2 percent to more than 20 percent.

Three features push someone into the higher-risk group:

• An abnormal serum free light chain ratio
• A non-IgG class of M protein
• A serum M protein of 1.5 g/dL or more

A Swedish cohort added a fourth, immunoparesis, meaning the other antibody classes are pushed down while the clone rises.

This is why a spike of 0.4 g/dL of IgG with a normal light chain ratio is watched, while a spike of 2.0 g/dL of IgA is worked up harder.

IgM clones behave differently. They point toward Waldenstrom macroglobulinemia and related lymphomas rather than classic myeloma. NCI describes amyloidosis with an IgM monoclonal gammopathy as a rare and distinct entity, with more nerve damage and more enlarged lymph nodes, and less heart involvement than other forms.

Find these five items and write them down with the date:

• The M protein size in g/dL from SPEP
• The heavy chain class and light chain type from immunofixation
• Kappa and lambda free light chains, and the ratio
• Hemoglobin, calcium, and creatinine from the same draw
• Whether a 24-hour urine study was done at all

Trend beats snapshot. One value cannot tell you whether the clone is stable, and repeat testing at set intervals is the point.

Some of these cannot wait for the next scheduled draw, and a few cannot wait at all.

• Call 911 or go to an emergency department if numbness or weakness spreads in your legs, your legs give way, or you lose control of your bladder or bowel. That combination can mean the spinal cord is being pressed on, and treatment within hours protects the ability to walk.
• Call 911 or go to an emergency department if you become confused or very drowsy, or cannot be woken properly. Calcium high enough to do that needs treating straight away.
• Call your care team the same day if you have unusual thirst with new constipation, pass much less urine than usual, or your legs swell.
• Call your care team within a day or two if bone pain is new, wakes you at night, or a bone breaks under minor force.

https://www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq

https://www.ncbi.nlm.nih.gov/books/NBK541035/

https://www.ncbi.nlm.nih.gov/books/NBK507880/