Smoldering Myeloma: When "Watch and Wait" Is the Right Treatment

Smoldering multiple myeloma (SMM) sits between monoclonal gammopathy of undetermined significance and active myeloma: an abnormal plasma cell population that is clearly significant but has not yet caused any organ damage. By international criteria it is defined by an M-protein above 3 g/dL, bone marrow plasma cells above 10% and below 60%, and the absence of any myeloma-defining event. Almost all active myeloma is preceded by this stage, with a median time to progression of roughly five years — but the range is enormous, from patients who never progress to those who progress within two years. The 2021 European Myeloma Network consensus addresses how to tell them apart and what to do.

Why it is usually observed, not treated

Treatment for myeloma is effective but not curative and carries toxicity, cost and long-term effects. Because a large proportion of people with SMM will not progress for many years — and some never will — starting therapy at the smoldering stage would expose many patients to treatment they do not need, without improving overall survival. Standard care is therefore active monitoring, aiming to catch the transition to active myeloma at the moment it happens, before organ damage occurs.

Risk stratification

Risk is estimated from the size and rate of increase of the M-protein, the percentage of bone marrow plasma cells, and the free light chain ratio, with several models in use — the Mayo Clinic model and the Spanish PETHEMA model among them, with the IMWG 2/20/20 criteria also widely applied. Cytogenetic abnormalities detected by FISH — particularly t(4;14), del(17p) and 1q gain — further refine risk. High-risk SMM carries a risk of progression of roughly 50% or more within two years, and this is the group in which treatment has been studied most actively.

Monitoring

Surveillance typically involves blood tests — full blood count, calcium, kidney function, M-protein, free light chains — at intervals of two to three months initially, extending to less frequent testing once stability is documented, together with clinical review for symptoms. Imaging is used to detect bone disease before it causes symptoms: whole-body low-dose CT, MRI of the spine and pelvis, or PET-CT, with the choice depending on availability and local practice; the consensus supports sensitive imaging at diagnosis and during follow-up, since an asymptomatic bone lesion is itself a myeloma-defining event. Bone marrow examination is repeated at intervals or when blood results change.

When treatment starts

Treatment begins when a myeloma-defining event occurs: the classic CRAB features — raised calcium, kidney impairment, anaemia, bone lesions — or the biomarkers that signal imminent organ damage: bone marrow plasma cells of 60% or more, a free light chain ratio of 100 or more, or more than one focal lesion on MRI. At that point standard myeloma therapy begins. For high-risk SMM, clinical trials of early intervention are the preferred route, and some centres offer early treatment outside trials after detailed discussion — but this should be an informed, individualised decision rather than a reflex.

Practical guidance

Ask: what is my risk category and which model was used, what imaging was done at diagnosis, how often will I be tested, and what specific change would start treatment? Learn the symptoms that should prompt an earlier appointment — new bone pain, especially in the back or ribs, unexplained fatigue, recurrent infection, or a fracture after minor trauma. Keep your own record of M-protein and light chain values, since the trend is often more informative than any single result.