Smoldering Myeloma (Smoldering Multiple Myeloma)

Where smoldering myeloma fits

Plasma cell disorders form a spectrum:

For an overview of all M-protein conditions, see monoclonal gammopathy.

Myeloma-defining events (CRAB)

Multiple myeloma is diagnosed, rather than smoldering myeloma, if the plasma cell disorder causes:

• Calcium elevation
• Renal (kidney) failure
• Anemia
• Bone lesions

Biomarkers that mean myeloma even without symptoms

Even without CRAB features, active myeloma is diagnosed if there is:

• 60% or more clonal plasma cells in the marrow
• an involved-to-uninvolved free light chain ratio of 100 or more
• more than one focal bone lesion on MRI

These features predict very high short-term progression risk, so treatment is started.

Risk of progression

Overall progression to myeloma is about 10% a year for the first 5 years, about 3% a year for the next 5, then about 1% a year. Risk depends on several factors. The Mayo 2/20/20 model uses:

1. M-protein above 2 g/dL
2. free light chain ratio above 20
3. marrow plasma cells above 20%

Certain genetic changes in the plasma cells (such as t(4;14), 17p deletion or 1q gain), rising M-protein over time, and abnormal imaging also increase risk.

Symptoms

By definition, smoldering myeloma does not cause organ damage. Most people have no symptoms and are diagnosed after an abnormal blood test. Some people report tiredness. New bone pain, anemia symptoms, kidney problems or infections should prompt reassessment for progression.

Diagnosis and staging tests

• Blood tests: serum protein electrophoresis, immunofixation, free light chains, complete blood count, calcium, creatinine, albumin and LDH
• 24-hour urine protein electrophoresis
• Bone marrow biopsy with genetic testing (FISH)
• Imaging: whole-body low-dose CT, PET-CT or whole-body MRI to look for bone lesions

Monitoring

• tests every 2 to 3 months for the first year, then every 4 to 6 months if stable (more often for high risk)
• repeat imaging periodically, or sooner if symptoms develop
• bone health: calcium and vitamin D, and assessment for osteoporosis

Treatment

• Low and intermediate risk: observation without treatment. Early treatment has not been shown to help, and it causes side effects.
• High risk: options include close monitoring, enrolling in a clinical trial, or early treatment. Trials have shown that lenalidomide, or the antibody daratumumab, can delay progression to active myeloma in high-risk patients, and these may be offered after discussion with a myeloma specialist.
• Bone protection with bisphosphonates is not routine for smoldering myeloma without osteoporosis.

Outlook

Many people with low-risk smoldering myeloma remain stable for many years. Those who progress are diagnosed early through monitoring, before serious organ damage, which improves outcomes. Treatment for multiple myeloma has improved greatly, with many people living for a decade or more after diagnosis.

Frequently asked questions

What is smoldering myeloma?

Smoldering myeloma is an early, symptom-free plasma cell disorder. It has higher levels of abnormal plasma cells or M-protein than MGUS but no organ damage such as anemia, kidney failure, high calcium or bone lesions. It can progress to multiple myeloma.

How is smoldering myeloma different from MGUS?

Both are precursors to myeloma without organ damage. MGUS has an M-protein under 3 g/dL and fewer than 10% marrow plasma cells. Smoldering myeloma has more, and a much higher yearly risk of progressing to myeloma.

How likely is smoldering myeloma to turn into multiple myeloma?

On average, about 10% of people progress each year in the first 5 years, then the risk falls. People with high-risk features, such as M-protein over 2 g/dL, free light chain ratio over 20 and more than 20% marrow plasma cells, have a much higher risk.

Is smoldering myeloma treated?

Usually not. Most people are monitored with regular tests. People with high-risk smoldering myeloma may be offered a clinical trial or early treatment with drugs such as lenalidomide or daratumumab, which can delay progression.

Is smoldering myeloma cancer?

Smoldering myeloma is considered an early, asymptomatic form of plasma cell cancer or a precancerous state, depending on the definition used. It does not cause damage at diagnosis, but it needs regular monitoring because it can progress.