An Overview of Smoldering Myeloma

Risk Factors, Symptoms, Diagnosis and Treatment

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Smoldering myeloma, also referred to as smoldering multiple myeloma (SMM), is considered a precursor to a rare blood cancer called multiple myeloma. It’s a rare disorder that is known for its absence of active symptoms. The only signs of smoldering myeloma are an elevation of plasma cells (in the bone marrow) and a high level of a type of protein called M protein that shows up in lab tests in the urine and blood. The reason the disorder is referred to as “smoldering” is that it often worsens slowly over time.

Although people with SMM are at risk for developing multiple myeloma, the progression of the disease does not always occur. In fact, over the first five years of being diagnosed with SMM, only about 10% progress to being diagnosed with multiple myeloma each year. After the first five years, the risk then drops to only 3% until the 10-year mark, when it further drops to 1%, according to the Multiple Myeloma Foundation.

Symptoms

M protein is an abnormal antibody produced by malignant plasma cells. Having high levels of M protein in the blood can lead to severe symptoms such as kidney damage, bone tumors, destruction of bone tissue, and immune system impairment. Having M protein levels in the blood at 3 g/dl or higher is one of the few signs of smoldering myeloma.

Other symptoms of smoldering myeloma include:

  • Absence of multiple myeloma symptoms (such as organ damage, bone fractures, and high levels of calcium)
  • Plasma cells in the bone marrow that are 10% or higher
  • A high level of light chains in the urine, also called Bence Jones protein (a protein made by plasma cells)

New Criteria for Assessing the Risk of Progression

Because the medical management of multiple myeloma can result in severe side effects, not everyone with smoldering myeloma should begin receiving treatment. Historically, there has been confusion among health practitioners when it comes to differentiating between those with smoldering myeloma who pose a high risk of going on to develop full-blown multiple myeloma, and individuals who have a low risk.

The need to accurately and consistently identify the risk level of individuals with smoldering myeloma created a dilemma for the healthcare industry. So, in 2014, new criteria were updated to unify the parameters around the risk of developing full-blown myeloma, for those with smoldering myeloma. 

The Lancet Oncology describes the updated criteria, and groups them as follows:

  • M protein level in the blood is over 3g/dl
  • Over 10% plasma cells are detected in the bone marrow
  • Free light chain (a type of immunoglobulin or protein in the immune system that functions as antibodies) ratio over eight or less than 0.125
  • No signs of symptoms including kidney failure, increased blood calcium level, bone lesions, or amyloidosis (a rare condition involving amyloid accumulation in the organs; amyloid is an abnormal sticky protein substance)

Low risk: A person is considered at low risk of progression from smoldering myeloma to multiple myeloma when only one of these signs or symptoms is present.

Intermediate risk: When two specific signs or symptoms are present, a person with smoldering myeloma is considered at intermediate risk (considered at risk of developing multiple myeloma in the next three to five years).

High risk: When a person has three of these signs, and no severe symptoms (such as kidney failure, increased blood calcium level, bone lesions or amyloidosis) it indicates a high risk that myeloma will develop within two to three years.

Individuals in the high-risk category are candidates for immediate treatment aimed at slowing down the progression of the disease and increasing the amount of time that a person with smoldering myeloma remains free of symptoms.

A 2017 study revealed evidence that survival rates may increase with early intervention and treatment of those in the high-risk category of SMM.

Causes

No one really knows what causes smoldering myeloma, but experts believe that there are several risk factors.

  • Genetic factors: Specific gene mutations that could be inherited may result in an increase in the number of plasma cells.
  • Age: The most common risk factor for smoldering myeloma or multiple myeloma occurs as a person ages, specifically between age 50 and 70 years old.
  • Race: If a person is African American, the risk of getting multiple myeloma, or smoldering myeloma doubles (compared to Caucasians).
  • Gender: Men are slightly more likely than women to get smoldering myeloma or multiple myeloma.
  • Obesity: Being overweight increases the risk of being diagnosed with smoldering myeloma or multiple myeloma.

Risk of Developing Other Conditions

Having smoldering myeloma can also raise a person’s risk of getting other disorders such as:

  • Peripheral neuropathy: A nerve condition which causes numbness or tingling in the feet or hands
  • Osteoporosis: A condition that results in softening of the bone tissue, leading to frequent bone fractures
  • Compromised immune system: This can result in frequent infections (and usually occurs in those who are in the high-risk category)

Diagnosis

Under most circumstances, smoldering myeloma is accidentally diagnosed. The healthcare provider may detect evidence of SMM when a lab test is conducted for other diagnostic purposes. The blood test or urine test may be high in M protein level or a blood test may show high plasma cell levels. 

With SMM there are no signs of symptoms of myeloma, which are sometimes referred to by using the acronym “CRAB:” high calcium levels (C), kidney problems (R), anemia (A) and bone damage (B).

Once a person is diagnosed with SMM, it’s important to visit the healthcare provider approximately every three months for ongoing blood and urine tests. This enables the physician to continue to evaluate the risk of the development of multiple myeloma. 

Diagnostic tests that may be used for ongoing observation of those with SMM may include:

  • Blood tests: To measure M protein levels
  • Urine tests: A 24-hour urine collection test may be ordered upon initial diagnosis and again two to three months after diagnosis.
  • Bone marrow biopsy tests: This involves a needle to aspirate the spongy tissue—in the middle of the bone—to be examined for myeloma cells.
  • Imaging tests (such as X-rays, PET, CT scans or MRIs): An initial series of imaging to record all the bones of the body, which are used to help the healthcare provider detect any abnormal changes down the road. MRIs are more accurate than X-rays at detecting signs and tracking the progression of bone damage.

Treatment

There is no cure for multiple myeloma. Treatment is recommended for those in the high-risk for developing multiple myeloma category.

Chemotherapy drugs include several types of medication to slow down the progression of the disease, such as Revlimid (lenalidomide) and dexamethasone. Early studies published by the Multiple Myeloma Research Foundation have shown that these drugs extended the time span in which those with smoldering myeloma in the high-risk category were kept from progressing to multiple myeloma. 

A new type of treatment is available for individuals in the high-risk category of SMM; this treatment involves drugs that support a person’s immune system and its ability to fight cancer. These drugs include Darzalex (daratumumab), ISA (isatuximab), and Keytruda (pembrolizumab). 

Clinical research studies are currently being conducted to discover data which will help to determine whether people with smoldering myeloma do better with early intervention and, if so, which treatment is most effective.

Coping

Receiving a diagnosis of a condition such as smoldering myeloma can be emotionally challenging for many people with SMM. It’s been described as “waiting for the other shoe to drop,” according to The Myeloma Crowd, a patient-driven, non-profit organization that empowers patients with rare diseases.

It’s important to seek out education and support. There are SMM online support groups and other resources that can help people with SMM to better understand and cope with the disease.

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  1. Muchtar E, Kumar SK, Magen H, Gertz MA. Diagnosis and management of smoldering multiple myeloma: the razor’s edge between clonality and cancer. Leukemia and Lymphoma. 2018 Feb;59(2):288-299. doi:10.1080/10428194.2017.1334124

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