Understanding Smoldering Multiple Myeloma: Its Nature and Progression

Introduction to Smoldering Multiple Myeloma (SMM)

Multiple myeloma is a type of blood cancer originating from abnormal plasma cells accumulating in the bone marrow. As these cells multiply excessively, they can crowd out healthy blood cells, leading to symptoms such as bone pain, fatigue, anemia, elevated calcium levels, and kidney problems.

Historical Context and Definition

The term "smoldering multiple myeloma" was first introduced in 1980 by Mayo Clinic hematologists Drs. Robert Kyle and Philip Greipp. It describes a stage where abnormal plasma cells are building up in the bone marrow but without causing noticeable symptoms. Despite the absence of symptoms, SMM shares many biological features with active multiple myeloma and carries a significant risk of progression.

Relationship with Other Conditions

Before developing SMM, patients often have a benign condition called monoclonal gammopathy of undetermined significance (MGUS). MGUS involves a small amount of abnormal plasma cells producing monoclonal proteins (M proteins) without symptoms. About 10% of MGUS cases eventually progress to SMM. When abnormal plasma cells continue to increase and acquire additional genetic abnormalities, MGUS can evolve into SMM.

Differentiating SMM from Active Myeloma

While SMM shares many features with active multiple myeloma, the key distinction lies in the absence of symptoms. Active myeloma typically presents with clinical complications, whereas SMM is asymptomatic. Advanced genetic analysis reveals that differentiating between high-risk SMM and early active disease can be challenging, as they often show similar biological characteristics.

Progression from SMM to Multiple Myeloma

Researchers are actively investigating when and how SMM progresses to active disease. The risk varies; some patients with low-risk SMM may remain asymptomatic for years, whereas those with high-risk SMM are more likely to develop full-blown myeloma within a shorter period. Approximately 50% of high-risk SMM patients are expected to progress within two years. However, the majority will eventually develop active multiple myeloma if left untreated.

Management and Surveillance

Current standard care involves active surveillance, monitoring for signs of disease progression. Patients diagnosed with MGUS or SMM should undergo evaluation at specialized blood disorder centers to determine their risk level. Second opinions are often advisable, especially when deciding whether intervention is necessary.

Screening and Early Detection

There are no routine screening recommendations for SMM, and it is usually diagnosed incidentally through blood tests detecting M proteins. Researchers continue to debate the benefits and risks of screening high-risk populations, such as individuals with family history or African ancestry, who may have a higher probability of developing the disease.

Emerging Treatments and Clinical Trials

Recent clinical studies have explored whether early treatment of high-risk SMM can delay progression to active myeloma. A notable trial published in December 2024 involved 390 patients: half received careful monitoring, and half received the drug daratumumab for three years. Results indicated that early intervention slowed disease progression and extended survival, with minimal impact on quality of life.

Future Perspectives

Dr. S. Vincent Rajkumar emphasizes that slowing the progression of SMM could delay — or potentially prevent — the onset of multiple myeloma. As clinical trials continue to evaluate the timing and methods of intervention, a future where treatment begins before symptoms emerge seems increasingly promising.

Conclusion

While more research is needed, understanding the biology of smoldering multiple myeloma is crucial. Advances in early detection and targeted treatment could significantly improve outcomes for patients at risk of developing this serious blood cancer.

source: https://medicalxpress.com/news/2025-04-smoldering-multiple-myeloma.html