Smoldering Myeloma

Smoldering myeloma is a precursor stage of multiple myeloma. Historically, smoldering myeloma patients have not been put on active treatment because many of them only  have a 10% risk per year for the first 5 years of progressing to active myeloma (with a cumulative 50% risk). Until treatment side effects become completely benign, it is critical for doctors to assess the likelihood of progression to know who will and won't progress in order to treat those who need it most.

One group that could benefit from treatment is the high-risk smoldering myeloma group. These patients are estimated to progress to active myeloma within 2 years of diagnosis. They typically have high risk myeloma genetic features or other conditions that show faster progression to active disease.

Having smoldering myeloma can be a mental challenge, waiting for the "other shoe to drop," so to speak. As smoldering myeloma patient Dana Holmes knows, it can be empowering to learn as much as you can in advance. (find the SMM FB group online and watch for a private message to confirm) There are emotional and mental benefits to understanding your disease and having a game plan.

But for many, the difference between smoldering myeloma and active myeloma can be confusing. In late 2014, the official criteria were updated for a smoldering myeloma diagnosis in Lancet Oncology. Here's a short description for those living with the uncertainty of a myeloma precursor condition.

Low Risk Smoldering Myeloma

According to Dr. Sagar Lonial of Emory University, if only one of these is present, a patient has low risk smoldering myeloma with a median to progression not reached with 10 year follow-up.

• Serum M protein level of more than 3 g/dL OR
• Free light chain ratio greater than 8 or less than 0.125 OR
• More than 10% plasma cells in bone marrow OR
• (No significant anemia, renal failure, hypercalcemia, bone lesions or amyloidosis)

Intermediate Risk Myeloma

If two of these are present, a patient has intermediate risk smoldering myeloma with an average between 3-5 years to progression to symptomatic myeloma. The intermediate risk has an average time of between 3 and 5 years to progression.

• Serum M protein level of more than 3 g/dL
• Free light chain ratio greater than 8 or less than 0.125 OR
• More than 10% plasma cells in bone marrow
• (No significant anemia, renal failure, hypercalcemia, bone lesions or amyloidosis)

High Risk Smoldering Myeloma

If all three of these are present, a patient has high-risk smoldering myeloma with an average between 2-3 years of progression.

• Serum M protein level of more than 3 g/dL
• Free light chain ratio greater than 8 or less than 0.125 OR
• More than 10% plasma cells in bone marrow
• (No significant anemia, renal failure, hypercalcemia, bone lesions or amyloidosis)

A new kind of smoldering multiple myeloma, termed light chain smoldering multiple myeloma, has been recently described in a study conducted at the Mayo Clinic, and the specific monoclonal protein level required for this diagnosis has also been added.

Smoldering myeloma patients should be observed and tested by their physician approximately every 3 months. Testing using blood tests, urine tests, bone marrow biopsy tests and imaging (PET-CT and MRIs) are all useful in the diagnosis of smoldering myeloma. Those who have bone lesions, osteoporosis or osteopenia may receive bisphosphonates.

The only opportunity to be treated with smoldering myeloma is to join a clinical trial. To find all smoldering clinical trials, click here:

Smoldering Myeloma Clinical Trials

Active Multiple Myeloma

Historically, it was considered to be active myeloma if the CRAB features were present. These include:

• C = Calcium (elevated) – hypercalcemia: Myeloma attacks bone, and as bone is broken down, it causes high calcium levels in the blood. This can cause a variety of symptoms, including excessive thirst, nausea, constipation, loss of appetite, and confusion.
• R = Renal failure: The most common cause of kidney failure in the myeloma patient is due to the proteins secreted by the malignant cells. Myeloma cells produce abnormally high levels of abnormal proteins in the blood. Depending on the size of these proteins, they may be excreted through the kidneys, which can cause damage. Additionally, increased bone loss leads to hypercalcemia, which can also contribute to kidney failure.
• A = Anemia: Anemia caused by myeloma results from the replacement of normal bone marrow by infiltrating tumor cells and inhibition of normal red blood cell production. Anemia can cause exhaustion, weakness, mental fatigue and forgetfulness.
• B = Bone lesions (bone pain): Bone pain affects a majority of myeloma patients, usually in the spine and ribs. Bone fractures and spinal cord compression is also common. The breakdown of bone also leads to the release of calcium in the blood, leading to hypercalcemia. It is common for bone problems to cause pain, breaks, and spinal problems.

In the revised 2014 criteria, three more markers are considered  “myeloma defining events” (MDEs).

• Over 60% of plasma cells in the bone marrow
• Serum involved / uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved free light chain is at least 100 mg/L (a patient’s “involved” free light chain – either kappa or lambda – is the one that is above the normal reference range; the uninvolved light chain is the one that typically is in, or below, the normal range)
• More than one bone lesion at least 5 mm in size on an MRI

According to Dr. Vincent Rajkumar on the Myeloma Beacon, the presence of at least one of these markers will be considered sufficient for a diagnosis of multiple myeloma, regardless of the presence or absence of symptoms or CRAB features.

Each of these markers has been shown in two or more independent studies to be associated with an approximately 80 percent or higher risk of developing myeloma-related organ damage within two years.

Stages of Multiple Myeloma