Smoldering Multiple Myeloma: Unveiling the Precursor to a Deadly Disease

Introduction

Smoldering multiple myeloma (SMM) is a subdivision of multiple myeloma (a type of blood cancer). The smoldering multiple myeloma is a precursor or an early sign that someone may or may not develop multiple myeloma (MM) later in life. However, smoldering multiple myeloma progresses slowly and may take years to become multiple myeloma. Patients with this condition may have no active symptoms, and the treatment may focus on preventing the disease from progressing.

What Is Smoldering Multiple Myeloma?

Smoldering multiple myeloma is a type of blood cancer, and the word smoldering means that the disease worsens with time as it progresses. It is a pre-cancerous stage involving abnormal proteins and high levels of plasma cells in the bone marrow. The main sign of the presence of SMM cells is the M-protein found in the blood. The M-protein is an abnormal antibody produced by cancerous plasma cells. This can be found by conducting a blood test. However, this condition does not show symptoms in every case and also does not resolve easily. It is the precursor of multiple myeloma, a condition in which white blood cells present in the immune system mutate into abnormal cells.

What Are Plasma Cells?

Plasma cells are a kind of white blood cell. These play an essential role in the immune system as they help in the production of antibodies that helps to fight certain conditions. Plasma cells also help control the immune response to a viral or bacterial infection. These are produced by B cells present in the bone marrow.

What Are the Causes and Risk Factors of Smoldering Multiple Myeloma?

According to various studies, it has been found that smoldering multiple myeloma occurs due to abnormal plasma cells and proteins in the bone marrow. However, the actual reason which leads to this abnormal conversion of plasma cells is not known. Some of the potential causes which are still under observation are as follows -

• Genetic Mutations - Research has been undergoing to find a connection between the mutation of oncogenes (cells that stimulate growth) and multiple myeloma or smoldering multiple myeloma.

• Obesity - Having high body fat levels is considered another causative factor of smoldering multiple myeloma.

Risk Factors - Smoldering multiple myeloma is a very rare disease. According to the researchers, it has been found that it is estimated to be seen in 1 in 100000 people. As the actual cause of smoldering multiple myeloma is unknown, some of the following risk factors can be considered for patients having this condition -

• Age - This condition is most commonly found in people of age 50 to 70 years.

• Race - Most commonly seen in black people.

• Sex - Males have a higher tendency to have this condition as compared to females.

• Genetics - Certain genetic mutations lead to high levels of plasma cells.

What Are the Symptoms of Smoldering Multiple Myeloma?

Smoldering multiple myeloma is an asymptomatic disorder that does not cause any symptoms in the patient. Therefore to diagnose this condition, doctors may perform blood tests. In the initial stage, there are no symptoms, but as the disease progresses to multiple myeloma, some of the following symptoms may be noticed which include -

• Brittle bones.

• Fatigue and weakness.

• Back pain.

• The problem in maintaining body balance.

• Infection.

• Confusion.

• Numbness or tingling in the extremities.

• Dizziness.

• Kidney problems.

What Are the Complications of Smoldering Multiple Myeloma?

There are no initial signs or symptoms seen in SMM; however, with time, the high levels of plasma cells and M-proteins can cause some serious complications, which may include -

• Bone Disorders - There is a significant risk of bone damage if smoldering multiple myeloma progresses to multiple myeloma. It has been seen that more than 80 percent of people with multiple myeloma have more than one bone disorder, such as osteoporosis. The rib cage, spine, and pelvis are the most commonly affected areas.

• Kidney Damage - High levels of M-protein can overload the kidneys. This can worsen with the calcium build-up. In severe conditions, it can lead to kidney failure as the kidneys are unable to filter the waste from the blood.

• Nerve Damage - The accumulation of M-protein can lead to peripheral neuropathy leading to numbness or tingling in the hands or feet.

• Weakened Immune System - The smoldering multiple myeloma can lead to high levels of antibodies that do not function properly, which can lead to frequent infections.

What Is the Diagnosis of Smoldering Multiple Myeloma?

Several tests may be conducted to confirm the diagnosis of smoldering multiple myeloma. The presence of M-protein in the blood or urine is considered a prime factor in diagnosing SMM. Moreover, some additional basic tests may also be conducted to confirm if the condition is progressing into multiple myeloma. Some of these tests include -

• Complete Blood Count (CBC) - This test helps in measuring the total count of red blood cells (RBCs), white blood cells (WBCs), and platelets that are produced by the bone marrow.

• Blood Chemistry Test - This test is done to check the levels of various enzymes or proteins in the body, such as

  • Creatinine Levels - To check the functioning of kidneys.

  • Albumin Levels - To check the functioning of kidneys and liver.

  • Calcium Levels - To check bone health.

  • Urine Tests - Urine can be tested to check for the presence of M-proteins.

• Quantitative Immunoglobulin Test - In this, the level of M protein is measured in the blood to confirm the diagnosis.

• X-rays - Healthcare providers may ask to get X-rays done to access the bone damage done by multiple myeloma.

• Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) Scan - These scans may also be used to look for bone damage by creating detailed images of the area.

• Bone Marrow Biopsies - Healthcare providers may do bone marrow biopsies by taking a sample from the bone marrow to assess the percentage of normal and abnormal plasma cells in the bone marrow. The bone marrow sample may also be accessed for any changes in the DNA (Deoxyribonucleic acid) that may indicate cancer growth.

What Do the Test Results Mean?

The lab blood tests conducted for the diagnosis of smoldering multiple myeloma may indicate the rate of progression by checking the levels of M-protein, plasma cells in the bone marrow, and free light chains (immune system proteins that function as antibodies).

In the test results, one point is given for every result indicating an elevated risk of the disease progression from two years of diagnosis.

Results -

• Serum M-protein: > 2 g/dL (grams per deciliter).

• Bone marrow plasma cells: > 20 percent.

• Serum-free light chain ratio: > 20.

The points are interpreted as -

• 0 Points: Low risk of progression.

• 1 Point: Intermediate risk of progression.

• 2 to 3 Points: High risk of progression.

What Is the Treatment for Smoldering Multiple Myeloma?

Presently there is no cure for smoldering multiple myeloma. However, certain treatment options are there to manage this condition and prevent other complications, such as -

• Chemotherapy Drugs - These drugs help in slowing down the progression of smoldering multiple myeloma to multiple myelomas, such as Lenalidomide and Dexamethasone.

• Monoclonal Antibodies - These are the newer drugs that help the immune system of the body to fight cancer, such as Daratumumab, Isatuximab-erfc, and Elotuzumab.

Conclusion

Smoldering multiple myeloma (SMM) is a precursor of multiple myeloma and a very rare condition. This can cause serious complications in the body, such as kidney damage, bone disorders, and an impaired immune system. There are no symptoms of this disease; therefore, it is challenging to identify this. However, during a routine blood examination, the presence of M-protein indicates this condition. The treatment of this condition focuses on preventing the progression of SMM to MM, which involves chemotherapy or other anti-cancer medications.