Smoldering multiple myeloma (SMM)

Plasma cells are white blood cells in the bone marrow that make antibodies. In smoldering myeloma, a group of abnormal plasma cells builds up and makes an abnormal antibody protein, called M protein or paraprotein. The National Cancer Institute (NCI) describes it as multiple myeloma that does not cause any signs or symptoms. It is often found by chance, on a blood or urine test.

It sits between MGUS and active myeloma. Compared with MGUS, there is more M protein or there are more abnormal plasma cells. The M protein is 3 g/dL or more in the blood, or at least 500 mg a day in the urine. Or plasma cells make up 10% to 60% of the marrow. But unlike active myeloma, there is no organ damage, no amyloidosis and none of the lab or scan findings that define active myeloma.

Smoldering myeloma always starts as MGUS, even when the MGUS was never found. Some people stay stable for many years. Others go on to active myeloma, which needs treatment.

Smoldering myeloma starts with DNA changes in plasma cells that happen during a person’s life. The exact cause is not known. Researchers think both genes and surroundings play a part.

It becomes more common with age, up to the late 70s in U.S. registry data, and is more common in men and in Black people. Having a close relative with MGUS, smoldering myeloma or myeloma slightly raises the chance. Myeloma Australia also lists immune conditions, some viruses, and certain chemicals or radiation as risk factors.

Some gene changes inside the abnormal plasma cells are linked with a higher chance of progression. These include t(4;14), t(14;16), a gain of chromosome 1q and a loss of chromosome 13.

By definition, smoldering myeloma causes no symptoms and no damage to the bones, kidneys or blood counts. Many people feel well and do not know they have it until a test shows it.

The concern is the chance of progression to active myeloma, or less often to AL amyloidosis. The NCI says rising anemia (a low red blood cell count) is the most reliable sign of progression. Other signs include new bone pain, a broken bone after little injury, kidney problems or high calcium.

The chance of progression depends a lot on risk. Doctors often use the 2/20/20 model. It counts three findings: an M protein above 2 g/dL, a free light chain ratio above 20, and more than 20% plasma cells in the marrow. Certain gene changes can be added. The more of these a person has, the higher the chance. The chance also falls the longer smoldering myeloma stays stable.

Smoldering myeloma is usually found by chance, or during regular checks for MGUS, when a blood or urine test shows a higher level of M protein. A blood specialist (hematologist) then orders more tests.

Blood and urine tests measure the M protein and free light chains. A blood count, calcium and kidney tests look for harm to the body. A bone marrow biopsy shows what share of the marrow is abnormal plasma cells, and gene tests (FISH) on the marrow look for higher-risk changes. Scans such as CT, PET-CT or MRI check the bones, because they can find damage that plain X-rays miss.

It is smoldering myeloma when the M protein is 3 g/dL or more in the blood (or at least 500 mg a day in the urine). Or it is when abnormal plasma cells make up 10% to 60% of the marrow. There must also be no amyloidosis and no myeloma-defining event. Those events include high calcium, kidney damage, anemia and bone lesions. They also include 60% or more plasma cells, a free light chain ratio of 100 or more, or more than one spot of 5 mm or larger on an MRI of the spine.

Most people with smoldering myeloma are not treated. Instead, they have active monitoring: regular blood and urine tests, with scans or a marrow test if results change. The NCI says people without bone lesions and with normal kidney function can be safely watched at first. Treatment usually starts if it turns into active myeloma.

For high-risk smoldering myeloma, one medicine is now approved. Daratumumab is an antibody that targets plasma cells. It is given as an injection under the skin, weekly at first and then less often, for up to 3 years. It was approved for this use in the European Union in July 2025. The U.S. FDA approved it (as Darzalex Faspro) for adults with high-risk disease in November 2025. The AQUILA trial included 390 people. After 5 years, 63% of those given daratumumab were alive without progression, compared with 41% of those who were monitored.

Experts still disagree about treating people who have no symptoms. Daratumumab can cause allergic and injection reactions, infections and low blood counts. It can also affect the tests blood banks use to match blood for a transfusion. Some experts argue that most progression events prevented in trials were test results rather than illness. Clinical trials are testing other approaches.

Living with smoldering myeloma usually means feeling well while having regular tests. Blood and urine tests track the M protein and free light chains. The care team sets how often, based on the risk group and how stable results are. Scans such as PET-CT or MRI can find bone damage that plain X-rays miss.

Watching and waiting can be hard. Myeloma Australia says people are often most anxious when first diagnosed and while waiting for test results. One person it quotes found that talking with a psychologist and with others living with smoldering myeloma helped. People who choose daratumumab have injections weekly at first, then less often.

Myeloma Australia asks people to report new symptoms right away, not wait for the next test. Warning signs include a broken bone after little or no injury and unexplained pain, especially in the back or ribs. Others are unexplained bruising or bleeding, feeling tired or breathless, and numbness or tingling in the hands or feet.

A stem cell transplant is not a standard treatment for smoldering myeloma itself, and no donor is involved. European transplant experts (EBMT) do not list it in their 2025 recommendations. NMDP names multiple myeloma, AL amyloidosis and POEMS syndrome as the plasma-cell disorders for which a transplant may be indicated.

Clinical trials have tested intensive myeloma treatment for high-risk smoldering myeloma. One phase 2 trial, GEM-CESAR, included a transplant with the person’s own stem cells. This is research, not standard care.

If smoldering myeloma becomes active myeloma, a transplant may then be part of treatment for people who are fit enough. EBMT says a first transplant with the person’s own cells remains the standard of care for younger people with myeloma. NMDP says most people with myeloma who have a transplant receive their own cells. It says donor transplants for myeloma are generally kept for high-risk disease.

Many people with smoldering myeloma stay stable for years, but the chance of progression varies a lot. An older Mayo Clinic study of people diagnosed in 1970–1995 found about a 10% chance a year in the first 5 years, 3% a year for the next 5, and 1% a year after that. Newer studies that use the 2014 criteria and modern scans report lower rates.

In a study of 308 people diagnosed at a New York cancer center in 2002–2019, about 30% had progressed within 5 years. The chance ranged from about 12% for low-risk to 67% for high-risk disease. In the AQUILA trial of high-risk smoldering myeloma, 93% of people given daratumumab and 87% of those monitored were alive 5 years after joining.