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Pre-Myeloma Explained

Pre-Myeloma Explained is a pillar page linking dozens of pre-myeloma focused blog posts on PeopleBeatingCancer. If you care to learn more about a pre-myeloma topic such as symptoms, staging, diagnostic testing, therapies etc. etc. simply click on the link to take you to a more in-depth explanation of the concept you want to learn about.

Pre-Myeloma is the term used to describe the pre-cursor stages of multiple myeloma which are:

Before we talk about pre-cursor stages of multiple myeloma, I have to briefly cover what it means to have monoclonal gammopathies. Monoclonal gammopathies are conditions in which abnormal proteins are found in the blood. The presence of  monoclonal gammopathies in your blood may or may not have anything to do with multiple myeloma.

According to research, approximately 55% of all monoclonal gammopathies are MGUS aka pre-myeloma.

This means that 45% of people diagnosed with monoclonal gammopathies should focus more on their symptoms and possible organ damage?

Keep in mind that the presence of monoclonal proteins in a person’s bone marrow, according to research, is one of the most common pre-cancers and occurs in approximately 3% of people over the age of 50 and more than 5% of the population over the age of 70. Further, the presence of monoclonal proteins in your bone marrow can indicate other health issues other than pre-myeloma.

While much of the research and writing on PeopleBeatingCancer focuses on the possible progression of monoclonal gammopathy to full multiple myeloma, it is possible that your diagnosis of  monoclonal gammopathy may lead to something else.

As a concept, the key difference between Monoclonal Gammopathy of Undetermined Significance (MGUS) and Monoclonal Gammopathy of Clinical Significance (MGCS) is the presence of disease or organ damage associated with the M-protein or to the clone itself, with therapeutic implications in the last one.

Therefore, individuals with MGUS are asymptomatic, without organ damage attributable to the clone or the M-protein, and without the need for treatment, whereas patients with MGCS are symptomatic, exhibit organ damage associated with the clone itself or the M-protein can be confirmed, and treatment may be needed.

Unfortunately, my experience is that the average oncologist knows little about monoclonal gammopathy issues other than it being a pre-myeloma stage. This means that if you are diagnosed with monoclonal proteins and have symptoms and organ involvement, you are likely to be told that you have MGUS and that your symptoms have nothing to do with have nothing to do with your MGUS diagnosis.

Published in 2012, this study below summarizes the traditional myeloma-focused medical understanding of plasma cell disorders.

“The plasma cell disorders are characterized by the proliferation of monoclonal plasma cells. These disorders include:

  • multiple myeloma;
  • Waldenström’s macroglobulinemia (WM);
  • immunoglobulin light chain (AL) amyloidosis;
  • solitary plasmacytoma of bone;
  • solitary extramedullary plasmacytoma;
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes);
  • plasma cell leukemia;
  • nonsecretory myeloma;
  • γ, α, and μ heavy-chain diseases;
  • monoclonal gammopathy of undetermined significance (MGUS);
  • and smoldering multiple myeloma (SMM)…”

The study linked below presents the more up-to-date, current understanding of monoclonal gammopathy as of the writing of this page (2023).

“Monoclonal gammopathy of clinical significance (MGCS) is an umbrella term to describe a broad spectrum of disorders with remarkable organ dysfunctions related to the underlying non-malignant B or plasma cell clone…

...Although the clone itself is typically very small, it is associated with diverse clinical manifestations through different mechanisms, such as monoclonal protein deposition, the biological activity of the monoclonal immunoglobulin, or angiogenic/inflammatory cytokine hyper-secretion (, ). Some predominantly involve

  • a single organ,
  • commonly peripheral nerves,
  • kidney,
  • or skin,

while others are systemic diseases with syndromic presentations. Recognizing the clinical features with appropriate workups, in particular tissue biopsies, are the key to making a timely diagnosis, especially when the kidney or skin is affected…”

Sadly, the article linked above doesn’t give much hope to the person with monoclonal gammopathy suffering nerve pain or some heath issue that is not understood by their oncologist.

My interpretation of articles that talk about MGCS is that the patient should focus on their symptoms (nerve, skin, kidney, etc.) and less on the possibility of progression to multiple myeloma. These articles simply talk about a “multidisciplinary approach” to therapy. Meaning, oncology will not offer possible therapies. But perhaps a neurologist will.

All I can say is that the study of monoclonal gammapathy of clinical significance is changing quickly and should offer solutions soon.

My point in explaining the two different sides to a monoclonal gammopathy diagnosis is three-fold:

  • First, MGUS can mean more than just being pre-myeloma. 
  • Secondly, patients are told that MGUS is asymptomatic. Yet monoclonal gammopathies can cause a host of symptoms. The good news is that symptoms may indicate organ damage which may indicate MGCS and you might not have to worry about multiple myeloma. You and your physician’s job is to figure out what your specific health issues involve. 
  • Thirdly, many patients diagnosed with MGUS are frustrated by painful symptoms. Oncology doesn’t diagnose or treat these symptoms enhancing the frustration of incorrectly diagnosed patients. 

Nerve involvement

From Biology to Treatment of Monoclonal Gammopathies of Neurological Significance

“Monoclonal gammopathy and peripheral neuropathy are common diseases of elderly patients, and almost 10% of patients with neuropathy of unknown cause have paraprotein. However, growing evidence suggests that several hematological malignancies synthesize and release monoclonal proteins that damage the peripheral nervous system through different mechanisms. The spectrum of the disease varies from mild to rapidly progressive symptoms, sometimes affecting not only sensory nerve fibers, but also motor and autonomic fibers.

Therefore, a multidisciplinary approach, mainly between hematologists and neurologists, is recommended in order to establish the correct diagnosis of monoclonal gammopathy of neurological significance and to tailor therapy based on specific genetic mutations…”

Kidney involvement-

Monoclonal Gammopathies of Renal Significance (MGRS)

“MGRS is basically defined as a kidney disease related to the presence of an M-protein, diagnosed by demonstration of monoclonal deposits in the kidney biopsy. Monoclonal deposits can consist of monoclonal LC, heavy chain, or intact Igs. Restriction to a single class of LC and/or heavy chain is mandatory [,,,,,]…”

Skin Involvement-

Monoclonal Gammopathies of Skin Significance

Some dermatologic entities are strongly associated with the presence of a Monoclonal Gammopathies, and they should be referred to as MGSS. Again, the demonstration of the association between the M-protein or the clone itself with skin damage is key. As expected, a skin biopsy plays a critical role in the diagnostic process.

The direct toxicity of M-protein, host immune abnormalities, specific cytokines, and Plasma Cell infiltration can, among other mechanisms, produce severe skin manifestations…”

Eye involvement

Monoclonal Gammopathies of Ocular Significance

The cornea is normally a transparent structure. Several abnormalities can cause corneal opacities, making vision difficult. Patients with Monoclonal Gammopathies should be included in the differential diagnosis of acquired corneal opacities, as this ocular finding could be the initial manifestation of a systemic disease that can potentially be life threatening.

As happens in other groups of MGCS with kidney or skin biopsies, corneal biopsy is of great diagnostic value. However, when it is not feasible due to the location of the corneal pathology, aqueous sampling may be an alternative approach for diagnostic purposes. The term MGOS was proposed for patients diagnosed with MGUS, in which the only significant clinical finding is ocular manifestation [,,,]. A regular, yearly ophthalmic checkup of these patients to improve their quality of life has been suggested.

Getting back to our focus on monoclonal gammopathies as pre-cursor stages of multiple myeloma.

SPB, MGUS and SMM are stages of pre-cancer for a blood cancer called multiple myeloma. According to research a diagnosis increases the patient’s risk of developing full multiple myeloma by 1% annually for MGUS and by approximately 10% annually for SMM.

Examples of other forms of pre-cancer are:

When people are diagnosed with pre-cancer for multiple myeloma, they often hear the word “cancer” and think the worst. While people should take this diagnosis seriously, the keys to understanding a diagnosis of pre-myeloma are that:

Conventional oncology often tells the newly diagnosed pre-myeloma patient that:

  • There is nothing that you can do to prevent progression to full myeloma and
  • To watch and wait

In the eyes of conventional medicine and the Food and Drug Administration, these two approaches are correct. The problem with these two statements is that there have not been any pre-myeloma therapies approved by the Food and Drug Administration shown to reduce the risk of a full myeloma diagnosis. Oncology’s instructions to watch and wait are a self-fulfilling prophecy.

Conventional oncology must follow the direction of the FDA. That’s the definition of board certification. However, if a newly diagnosed pre-myeloma patient looks beyond conventional FDA approved oncology, he/she can learn about possible causes, possible symptoms, diagnostic testing, therapies and more.

Possible causes of pre-myeloma?

Most of us who have been diagnosed with a form of pre-myeloma wonder how we developed this odd, rare, blood disorder. Because pre-myeloma is not cancer, little research has been done on the possible causes of it. Further, oncology theorizes that multiple myeloma is preceded by monoclonal gammopathy. My point is that studies that cite possible causes of multiple myeloma are, by definition, causes of pre-myeloma.

To Learn More about the possible causes of both pre and full myeloma- click now

Pre-Myeloma Symptoms- one of the most frustrating aspects of a diagnosis of pre-myeloma is that oncology considers them to be asymptomatic aka without symptoms. Yet as many patients living with a SPB, MGUS or SMM know, pre-myeloma can be rife with symptoms.

Any symptoms you have can be a useful indicator of what type of pre-myeloma you are dealing with. Symptoms coupled with diagnostic testing results can lead you and your oncologist to the answers you are looking for.

Diagnostic Testing-

A diagnosis of a pre-myeloma stage- a single plasmacytoma of bone, monoclonal gammopathy of undermined significance or smoldering multiple myeloma, is a double-edged sword. On the one hand, you will live with regular diagnostic testing for the rest of your life. On the other hand, knowledge is power and you can change your diet and lifestyle to reduce your risk of a multiple myeloma diagnosis.

Evidence-based, non-conventional pre-myeloma therapy-

If a therapy, despite research, has not been approved by the Food and Drug Administration, conventional oncology will not prescribe it. PeopleBeatingCancer disagrees with this approach. Research shows that anti-angiogenic nutrition, supplementation, exercise, whole body hyperthermia and more are cytotoxic to monoclonal proteins.