What Is Smoldering Multiple Myeloma

Overview

Definition of smouldering multiple myeloma (SMM)

Smouldering multiple myeloma (SMM) is a plasma cell disorder that is indicative of multiple myeloma (a type of bone marrow cancer) and is characterised by the presence of abnormal plasma cells in the bone marrow.¹ To understand SMM, we must first understand the role of the plasma cells in the body, and how abnormalities in plasma cells could potentially lead to cancer. Read on to find out more about multiple myeloma and SMM.

Plasma cells and multiple myeloma

Plasma cells are a type of white blood cell that develop from B lymphocytes and made in the bone marrow. They are a critical component of the immune system, and are responsible for producing antibodies that defend the body against infections and disease.² If these plasma cells become abnormal (myeloma cells), it can lead to a cancer known as multiple myeloma (MM). 

MM is a disease in which abnormal plasma cells uncontrollably multiply in the bone marrow.² The bone marrow is where stem cells mature into different types of blood cells, such as:²

• Red blood cells – carry oxygen around the body
• White blood cells – defend the body against infection and disease
• Platelets – form blood clots to stop or prevent bleeding

Symptoms of multiple myeloma

A build-up of myeloma cells in the blood marrow interferes with the production of healthy blood cells, leading to a decreased number of red blood cells, white blood cells and platelets. As these myeloma cells accumulate, they produce an excess amount of a particular type of antibody known as monoclonal protein.¹ This accumulation can eventually lead to a number of symptoms, such as:

• Bone pain
• Anaemia
• Fever
• Easy bruising/bleeding
• Breathing difficulties/ shortness of breath
• Fatigue²

Additionally, myeloma cells can damage and weaken the bone. This can cause hypercalcaemia, a condition where there is too much calcium in the blood, which can lead to many other secondary symptoms such as:

• Nausea or vomiting
• Frequent thirst
• Frequent urination
• Muscle weakness
• Loss of appetite
• Kidney issues²

What is smouldering multiple myeloma

As mentioned before, smouldering multiple myeloma (SMM) is a plasma cell disorder and a precancerous condition that is indicative of a type of bone marrow cancer called multiple myeloma. SMM is an asymptomatic condition and as such, it does not cause symptoms associated with multiple myeloma, hence why it is referred to as ‘smouldering’ because it represents a latent stage of the disease.¹ 

How SMM differs from symptomatic multiple myeloma

SMM differs from symptomatic multiple myeloma in terms of clinical presentations i.e. the symptoms that individuals with either condition experience. Multiple myeloma is characterised by various symptoms such as fatigue,bone pain etc., whereas SMM lacks these noticeable signs.³ It is this distinction between the two conditions that makes early detection and monitoring critical to prevent the progression of SMM to multiple myeloma. 

Prevalence and incidence statistics

SMM is relatively rare, accounting for around 0.4-0.9 cases per 100,000 people but its exact prevalence and incidence varies amongst different populations and regions.⁴ However, understanding the prevalence and incidence of SMM is crucial for healthcare planning and early intervention. This is because it represents a critical stage in the progression of multiple myeloma, and detecting it early can significantly impact treatment outcomes and patient health.

Risk factors for SMM

There are many factors which may increase an individual’s risk of developing SMM such as:

• Family/personal medical history – Those with a history of plasma cell disorders or other precancerous conditions, whether in their family or personal history, may be more likely to develop SMM
• Environmental factors – Exposure to toxins or radiation may contribute to the risk of developing SMM
• Genetic predispositions – A person’s genetic makeup could make them more susceptible to developing SMM
• Age – The risk of developing SMM increases with age, with most cases diagnosed in individuals over 60 years of age
• Gender – SMM is slightly more common in people assigned male at birth than people assigned female at birth^,6

Diagnosis

Diagnosis criteria

As SMM does not usually cause symptoms, it may be discovered by chance following routine healthcare checks or blood tests for other conditions if elevated levels of abnormal plasma cells or monoclonal protein is detected.¹⁷ For a patient to be diagnosed with SMM, they must meet certain diagnostic criteria i.e. having a certain percentage of abnormal plasma cells in the bone marrow and a specific monoclonal protein level. 

Common medical tests

The diagnosis of SMM usually involves a series of medical tests and evaluations such as^]:

• Blood/urine tests – Blood or urine samples are taken from the patient, and the levels of monoclonal protein made by the myeloma cells are measured.
• Bone marrow biopsies – A small sample of bone marrow is removed by inserting a hollow needle into a bone, such as the hipbone or breastbone. This sampleis then checked under a microscope by a pathologist to look for abnormal cells.
• MRI scans (magnetic resonance imaging) – This procedure uses magnetic fields and radio waves to produce detailed images of areas inside the body and may be used to find damaged or weakened bone.
• Skeletal bone survey – In this survey, X-rays of all the bones in the body are taken and used to find areas of damaged or weakened bone.^1,2

Early studies and treatment

Several studies have been conducted that evaluated the use of drugs to prevent SMM progression to multiple myeloma. Melphalan is a chemotherapeutic drug that works by interfering with the growth of cancerous cells, and prednisone is a corticosteroid, which has anti-inflammatory effects.^8,9 Three small studies looked into the impact of starting early treatment with melphalan and prednisone on overall survival in individuals with SMM.¹ They compared this approach to observation alone or treatment at the time of progression using melphalan and prednisone. However, researchers did not find significant improvement in overall survival with early therapy for individuals with SMM.¹  

Bisphosphonates are a group of drugs that strengthen the bones and slow bone loss.¹⁰ A bisphosphonate called pamidronate has been studied for its effects against observation alone for SMM treatment.¹ Again, there was no improvement in overall survival with pamidronate administration.

Importance of close medical monitoring

Because clinical trials have not produced clear data on the benefits of early therapy, treatment strategies for SMM are focused on observation as the standard of care for patients.¹¹ Regular medical check-ups and monitoring is essential for individuals at risk of SMM, particularly for patients with a genetic predisposition or other risk factors. Because SMM can remain asymptomatic for extended periods, early detection through regular blood tests and medical monitoring is the key to preventing its progression to symptomatic multiple myeloma.

Progression to symptomatic multiple myeloma

SMM poses a risk of progressing to active multiple myeloma over time, but the likelihood of this progression varies among individuals. Some patients with SMM can remain stable for years without their condition progressing, while others may experience a faster progression. The exact chance of SMM evolving into symptomatic multiple myeloma depends on various factors such as:¹²

• The level of abnormal plasma cells in the blood marrow
• The proliferation rate of abnormal plasma cells i.e., how fast the plasma cells increase in number
• The quantity and protein type of monoclonal protein in the blood
• The overall health and age of the individual
• Genetic characteristics of the individual

Regular check-ups, blood tests, and bone marrow examinations are essential for tracking disease progression from SMM to multiple myeloma. Early detection of any signs of progression allows for timely intervention and treatment, improving the prognosis and quality of life. The role of healthcare providers, such as haematologists, oncologists, pathologists, and other medical experts play a crucial role in making informed decisions about the best course of action.

Summary

Smouldering multiple myeloma (SMM) is a precursor to multiple myeloma, characterised by the presence of abnormal plasma cells in the bone marrow. Understanding the role of plasma cells in the body and the potential transformation of these cells into cancer is essential. Multiple myeloma, a condition where these abnormal plasma cells multiply uncontrollably, can lead to various symptoms, including bone pain, anaemia, and weakened bones. SMM differs from symptomatic multiple myeloma due to its lack of noticeable symptoms, emphasising the need for early detection and monitoring.

Various risk factors, such as genetic predisposition, environmental factors, and age, can increase the chance of developing SMM. Diagnosis involves various medical tests, including blood and urine tests, bone marrow biopsies, MRI scans, and skeletal bone surveys, which help confirm the diagnostic criteria for SMM.

While some studies have explored early treatment with drugs like melphalan and prednisone, no significant improvement in overall survival has been observed with this approach. As a result, the standard of care for SMM involves regular medical check-ups and monitoring. The risk of SMM progressing to symptomatic multiple myeloma varies among individuals. It depends on factors such as the level of abnormal plasma cells, the quantity and type of monoclonal protein, and overall health.

Close work with healthcare providers is vital for making informed decisions regarding the management of SMM. In the landscape of current SMM research, early detection isy the key to preventing its progression to symptomatic multiple myeloma and improving patient outcomes.