What Does an M-Spike Mean?

Blood plasma is full of antibodies. Normally thousands of different plasma cells each make a slightly different one. On serum protein electrophoresis, a lab test that separates proteins by electrical charge, that variety shows up as a broad, low hump.

An M-spike is what happens when one plasma cell clone takes over part of that output. Every copy is identical, so instead of a hump the tracing shows a narrow peak. M stands for monoclonal, meaning one clone. The protein itself is called an M protein, a monoclonal protein, or a paraprotein.

The spike is a finding, not a disease. Electrophoresis says a clone exists and roughly how much protein it makes. It does not say what the clone is doing. Two further tests answer that. Immunofixation names the class, such as IgG kappa or IgA lambda. A serum free light chain assay measures the loose kappa and lambda chains and gives their ratio.

NCI's definition is precise. In monoclonal gammopathy of undetermined significance, there is an M protein in the serum. There is no myeloma, macroglobulinemia, amyloidosis, or lymphoma. And fewer than 10% of the cells in the bone marrow are plasma cells.

NCI's guidance on what to do is equally plain. People with MGUS are asymptomatic. They do not need to be treated.

The reason it is still followed is a sentence worth reading twice. Virtually all cases of multiple myeloma are preceded by a slowly rising MGUS. But most MGUS never gets there. NCI puts the annual risk of progression to a lymphoid or plasma cell cancer at 0.5% to 1.0% in population-based groups. In higher-risk groups it ranges from 2% to more than 20% a year. Myeloma is the most common destination. Amyloidosis, lymphoplasmacytic lymphoma, and chronic lymphocytic leukemia are others.

NCI lists three features that predict progression, and they are the reason two people with the same spike can be given different schedules.

The first is an abnormal serum free light chain ratio. The second is a non-IgG class of MGUS, so IgA or IgM rather than the more common IgG. The third is a serum M protein level of 1.5 g/dL or higher.

A Swedish cohort study confirmed the first and third, and added a fourth: immunoparesis. That means the other antibody classes are pushed down. With an IgG kappa M protein, immunoparesis would show as IgA and IgM below normal.

None of these is a diagnosis. They set how closely the picture is watched, and they explain why a level and a ratio matter more than the word "spike."

The next categories have numbers attached, and they are worth knowing because they are what a hematologist is checking against.

Smoldering myeloma requires a serum IgG or IgA M protein of at least 30 g/L, or urinary monoclonal protein of at least 500 mg per 24 hours. It also requires clonal marrow plasma cells of 10% to 60%. Above 60% is overt myeloma.

Active myeloma, in the International Myeloma Working Group criteria NCI reprints, is defined by any one of these: amyloidosis, calcium more than 1 mg/dL above the reference range, creatinine above 2 mg/dL or creatinine clearance under 40 mL/min, hemoglobin below 10.0 g/dL, one or more bone lesions on skeletal imaging or PET-CT, clonal marrow plasma cells at 60% or more, an involved to uninvolved free light chain ratio of 100 or more, or more than one focal lesion of at least 5 mm on MRI.

That list is the reason an M-spike triggers a calcium, a creatinine, a hemoglobin, and imaging. The spike alone decides nothing. The organ findings decide everything.

There is also a risk score for smoldering disease. The IMWG 2/20/20 rule counts M protein above 2 g/dL, a free light chain ratio above 20, marrow plasma cells above 20%, and certain chromosome changes. Three or four of those predict a greater than 50% chance of progression within 2 years.

After myeloma is confirmed, the M protein stops being a clue and becomes a ruler. Response criteria are written in terms of it. A very good partial response means the serum monoclonal protein has fallen by 90% or more, with 24-hour urine monoclonal protein under 100 mg. A complete response requires negative immunofixation as well as a clear marrow. When the free light chain levels and ratio also return to normal, that is called a stringent complete response.

This is why the same number appears on every follow-up report. It is being tracked as a trend, not read as a single value.

There is one important exception to "MGUS does not need treatment." A monoclonal gammopathy that damages an organ needs therapy regardless of how small the clone is.

The kidney version has its own name: monoclonal gammopathy of renal significance. NCI describes the markers followed for it — rising serum creatinine, falling glomerular filtration rate, and rising urinary albumin. The heart and the peripheral nerves can be affected too. N-terminal pro-brain natriuretic peptide is a very sensitive marker for cardiac amyloid involvement, though NCI notes its specificity is low.

Expectations should be set carefully here. In a review of 6,399 people with newly diagnosed myeloma, 44 had a separate biclonal IgG or IgA MGUS. The myeloma clone responded to induction 93% of the time. The separate MGUS clone responded 64% of the time.

For the diseases behind these numbers, see multiple myeloma and smoldering myeloma and MGUS. For how the marrow result is worded, see what bone marrow involvement means.

• NCI PDQ — Plasma Cell Neoplasms Including Multiple Myeloma Treatment (Health Professional Version)
• NCI PDQ — Plasma Cell Neoplasms Including Multiple Myeloma Treatment (Patient Version)