M-Spike in Multiple Myeloma: Understanding Significance

M-Spike in Multiple Myeloma: What Does Your Monoclonal Protein Level Mean?

M-Spike in Multiple Myeloma: What Does Your Monoclonal Protein Level Mean? If you have been diagnosed with multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), or smoldering multiple myeloma (SMM), you will probably hear the term “M-spike” again and again.

Your doctor may say:

“Your M-spike is 3.0.”
“Your M-spike has dropped to 0.5.”
“We can no longer detect an M-spike.”
“Your M-spike is beginning to rise.”

But what exactly is an M-spike?

And perhaps more importantly, what does an M-spike tell you about your multiple myeloma?

The short answer is that an M-spike is a laboratory measurement associated with a monoclonal protein, also called an M-protein, monoclonal immunoglobulin, myeloma protein, or paraprotein.

The M-spike can be an important way of measuring and monitoring multiple myeloma, but it is not the same thing as the amount of cancer in your body and it should never be interpreted by itself.

My name is David Emerson. I am a long-term survivor of multiple myeloma. When my oncologist told me that I was “non-secretory,” I had no idea what he was talking about…

I believe that MM patients will benefit from clearly understanding the complicated medical jargon that surrounds their blood cancer diagnosis. This post is my effort to explain the term

M-spike
Monoclonal Protein
M-protein

In the post below, I’ve combined my explanations with questions from MM patients with explanations from the NCI, ACS, etc.

Further, my research and experience with evidence-based non-conventional therapies are the reason why I have lived in complete remission from my incurable blood cancer since achieving complete remission in early 1999. I have learned that the best way to manage multiple myeloma is to combine the best of conventional and evidence-based non-conventional therapies.

Chances are your oncologist won’t talk to you about evidence-based non-conventionaltherapies. Conventional oncology focuses on FDA-approved therapies. That’s what they do. But I believe that MM patients and survivors need to know the basics of conventional, complementary, and integrative therapies linked below to manage their incurable blood cancer.

Scroll down the page and post a question or a comment if there’s anything you’d like to know about MM.

Good luck,

David Emerson

Concepts Central to Managing Your Cancer-

Possible Therapies-

What Is an M-Protein?

Plasma cells are specialized white blood cells that normally produce antibodies to help the immune system fight infections.

In multiple myeloma and related plasma-cell disorders, one abnormal group—or clone—of plasma cells produces an abnormal immunoglobulin called a monoclonal protein or M-protein.

The National Cancer Institute defines M-protein as an antibody found in unusually large amounts in the blood or urine of people with multiple myeloma and other plasma-cell tumors.

You may hear several different terms for essentially the same thing:

M-protein
M-spike
monoclonal protein
monoclonal immunoglobulin
myeloma protein
paraprotein

The terms are related, but there is an important distinction:

M-protein is the abnormal protein itself. M-spike describes the way that protein appears on a protein-electrophoresis test.

The International Myeloma Foundation explains that the monoclonal protein appears as a sharp spike on protein electrophoresis because the proteins produced by the abnormal plasma-cell clone are sufficiently similar that they migrate together during the laboratory test.

International Myeloma Foundation: M-Protein Testing Guide

Why Is It Called an “M-Spike”?

One of the most common tests used to look for and measure an M-protein is serum protein electrophoresis (SPEP).

SPEP separates proteins in a blood sample according to their physical and electrical characteristics.

When a monoclonal protein is present, it can appear as a narrow, relatively distinct peak on the laboratory graph.

That is the M-spike.

The American Cancer Society explains that electrophoresis can identify the abnormal antibody and that the protein may be called monoclonal immunoglobulin, M-protein, M-spike, or paraprotein.

So when a patient says:

“My M-spike is 1.2.”

they are generally referring to the quantity of monoclonal protein measured by the laboratory—not to a measurement of the number of myeloma cells.

What Does an M-Spike Tell You About Multiple Myeloma?

An M-spike can provide valuable information about the activity of a patient’s plasma-cell disorder.

For example, if a patient begins treatment with a measurable M-protein and the M-spike subsequently falls substantially, that can be evidence that the treatment is reducing the measurable disease marker.

Conversely, a sustained increase in M-protein can warn that the underlying plasma-cell disorder may be becoming more active.

The National Cancer Institute notes that patients with M-protein are evaluated by measuring and following the serum M-protein, along with other laboratory and clinical findings.

But there is an important caveat:

Your M-spike is not your entire myeloma story.

Multiple myeloma is a complicated disease.

Doctors may also monitor:

Serum free kappa and lambda light chains
Free-light-chain ratio
Immunofixation electrophoresis
Complete blood count
Hemoglobin
Creatinine and kidney function
Calcium
Albumin
Beta-2 microglobulin
Bone marrow plasma-cell percentage
PET/CT, MRI, or other imaging
Minimal residual disease (MRD) testing
The NCI specifically describes M-protein measurement as one component of the broader evaluation of plasma-cell disorders.

Does a Higher M-Spike Mean More Myeloma?

Not necessarily.

This is one of the most important things for a newly diagnosed patient to understand.

M-protein production varies considerably among people with myeloma.

Some patients have plasma cells that produce substantial quantities of M-protein. Other patients produce relatively little. And some patients have non-secretory or very-low-secretory myeloma, meaning that conventional M-protein testing may provide little or no measurable marker of disease.

The International Myeloma Foundation notes that myeloma patients can be high producers, low producers, or non-secretors of monoclonal protein.

Therefore:

A large M-spike does not automatically mean that a patient has more dangerous myeloma, and a small M-spike does not automatically mean that the disease is harmless.

The clinical context matters.

Can You Have Multiple Myeloma Without an M-Spike?

Yes.

This is particularly important for patients who have been told that their M-spike is “undetectable.”

An undetectable M-spike does not necessarily mean that there are no myeloma cells.

Some patients have disease that produces very little measurable M-protein. Others may have predominantly light-chain disease. Still others may have non-secretory myeloma.

This is why doctors can use additional tests such as serum free-light-chain testing, immunofixation, bone marrow examination, imaging, and MRD testing.

PeopleBeatingCancer has a separate article on this issue:

What Is Non-Secretory Myeloma?

That article is particularly important for patients who are confused by having a multiple myeloma diagnosis despite having little or no measurable M-spike.

M-Spike, MGUS and Smoldering Multiple Myeloma

An M-protein does not automatically mean that a person has active multiple myeloma.

Monoclonal proteins can occur in several plasma-cell disorders, including:

MGUS
Smoldering multiple myeloma
Multiple myeloma
Plasmacytoma
Some other plasma-cell disorders

The Mayo Clinic explains that MGUS is characterized by altered plasma cells producing monoclonal proteins, and that MGUS is different from active multiple myeloma.

Similarly, people with smoldering multiple myeloma can have an M-protein without having the organ damage or other myeloma-defining features associated with active disease.

This is why you cannot diagnose active multiple myeloma simply by looking at an M-spike number.

What If My M-Spike Is Rising?

A rising M-spike deserves attention, but the meaning depends on the circumstances.

For someone with MGUS, a rising M-protein may indicate increasing risk of progression and may lead to additional testing.

For someone with smoldering myeloma, changes in M-protein can be one component of assessing the risk of progression to active disease.

For someone previously treated for multiple myeloma, an increasing M-protein may indicate biochemical progression or relapse.

The International Myeloma Foundation describes biochemical relapse as progression demonstrated by increasing M-protein without symptoms or organ dysfunction.

However, one abnormal laboratory result does not necessarily mean that your myeloma has relapsed.

Doctors generally look for a meaningful and reproducible change rather than reacting to every small fluctuation.

What If My M-Spike Goes Down?

A declining M-spike is generally encouraging when the M-protein is a reliable marker of your disease.

For example, a patient whose M-spike falls from 4.0 to 1.0 following treatment has experienced a substantial reduction in measurable monoclonal protein.

But again, the M-spike is only one part of the assessment.

A patient may have a low or undetectable M-spike while still having measurable disease detectable through other testing.

Conversely, a small residual M-spike does not necessarily mean that treatment has failed.

The depth and durability of response are evaluated using multiple measurements.

What Does “No M-Spike” Mean?

Patients often hear the phrase “no M-spike detected” and understandably interpret it as meaning that their myeloma is gone.

That interpretation can be too simplistic.

“No M-spike detected” means that the laboratory did not detect a measurable monoclonal spike using that particular testing method.

Depending on the circumstances, additional testing may include immunofixation, free-light-chain testing, bone marrow examination, imaging, or MRD testing.

This distinction becomes particularly important as increasingly sensitive technologies are used to detect very small amounts of monoclonal protein.

Mayo Clinic Laboratories, for example, now describes mass-spectrometry-based testing designed to identify M-proteins with greater analytical sensitivity than traditional electrophoresis in some circumstances.

M-Spike vs. Total Protein

Another common source of confusion is the difference between total protein and M-protein.

They are not the same test.

Total protein includes many different proteins circulating in your blood.

An M-protein is one abnormal monoclonal protein produced by a clone of plasma cells.

PeopleBeatingCancer has previously addressed this issue in:

Is Total Protein the Same as M-Protein?

Understanding this distinction can prevent a great deal of unnecessary confusion when reading your blood-test results.

M-Spike and Free Light Chains Are Not the Same Thing

Another important distinction is between an M-spike and serum free light chains (FLCs).

Antibodies are made from heavy and light chains. Some plasma-cell disorders produce intact immunoglobulins that can be measured as an M-protein. Other patients produce predominantly light chains.

That means the M-spike and free-light-chain measurements can sometimes behave differently.

PeopleBeatingCancer’s article:

Free Light Chains- Myeloma

provides a more detailed explanation of this important myeloma marker.

Six PeopleBeatingCancer Articles About M-Spikes

1. M-protein, M-spike in Myeloma?

The post linked below is one of the strongest supporting articles because it directly addresses the terminology and explains the relationship among M-protein, M-spike, monoclonal protein, and paraprotein.

2. Multiple Myeloma Blood Counts Climbing- M-spike, FLC’s, Low Platelets…

This post is particularly useful for patients who are watching several laboratory markers simultaneously, including M-spike and free-light-chain levels.

3. Elevated IGG, no M-spike, Dx of MGUS- Thoughts?

This post provides an excellent opportunity to explain why an elevated immunoglobulin level and an M-spike are not necessarily interchangeable findings.

4. MGUS Dx, M-spike of .3 now up to .5- “I’m worried…”

This post is especially valuable for the MGUS → SMM → multiple myeloma portion of the cluster because it addresses the anxiety that can accompany a rising M-spike.

5. SMM Progression- M-spike and FLC are key

This post is an important supporting article for patients with smoldering multiple myeloma who want to understand how changes in M-protein and free-light-chain measurements may relate to progression risk.

6. Multiple Myeloma Relapse? Dec. M-spike, Inc. Freelight Chains…

This article gives the cluster a natural relapse/recurrence component and addresses the sometimes-confusing relationship between M-spike and free-light-chain measurements.

Three Reliable Sources for Understanding M-Protein

Patients who want a more conventional medical explanation should also be directed to these resources.

National Cancer Institute

The NCI’s definition of M protein explains that it is an antibody found in unusually large amounts in the blood or urine of people with multiple myeloma and other plasma-cell tumors.

NCI — Definition of M Protein

Mayo Clinic

Mayo Clinic’s explanation of smoldering multiple myeloma discusses monoclonal protein/M-protein and explains how it fits into the spectrum of plasma-cell disorders.

Mayo Clinic — Smoldering Multiple Myeloma

American Cancer Society

The American Cancer Society explains the terminology surrounding monoclonal immunoglobulin, M-protein, M-spike, and paraprotein and also explains how electrophoresis is used to detect these proteins.

American Cancer Society — What Is Multiple Myeloma?

The Bottom Line About Your M-Spike

The M-spike is one of the most familiar numbers in the world of multiple myeloma.

It can help doctors and patients understand whether measurable monoclonal protein is increasing, decreasing, or remaining stable.

But your M-spike is not a stand-alone measurement of your cancer.

A better way to think about it is:

M-spike = one important piece of the myeloma puzzle.

Your oncologist or hematologist may need to consider your M-spike together with free-light-chain results, immunofixation, blood counts, kidney function, calcium, imaging, bone marrow findings, symptoms, and—when appropriate—MRD testing.

Perhaps the most important question is therefore not:

“What is my M-spike?”

but:

“What does my M-spike mean when considered together with all of my other myeloma tests?”

That is the question that can help you understand where your disease stands today and what your doctors are watching for next.

PeopleBeatingCancer Evidence Rating

Evidence Rating: ★★★★★ Strong

The basic explanation of M-protein, M-spike, electrophoresis, and the role of monoclonal protein in plasma-cell disorders is well established by the National Cancer Institute, Mayo Clinic, American Cancer Society, International Myeloma Foundation, and International Myeloma Working Group–based laboratory guidance.

Important: An individual patient’s M-spike should be interpreted by their treating hematologist/oncologist in the context of the patient’s complete laboratory, imaging, bone-marrow, and clinical findings.

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