Early Intervention Strategies in High-Risk Smoldering Multiple Myeloma
Key Points
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Smoldering multiple myeloma is categorized as low- or high-risk using models like Mayo Clinic’s 20/20/20 rule to help identify patients who may benefit from early treatment.
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Patients meeting high-risk criteria have about a 46% two-year progression rate, supporting consideration of early intervention with agents such as daratumumab.
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Evolving disease markers and high-risk cytogenetics also inform decisions on initiating therapy versus continued active surveillance.
In an interview at the 2025 ASH Annual Meeting, Jing Wang, MD, of Wilmot Cancer Institute, sat down with Anuja Abhyanker, MD, of Roswell Park Comprehensive Cancer Center, to discuss strategies for managing smoldering multiple myeloma.
Smoldering multiple myeloma remains a heterogeneous category between MGUS and active myeloma, and careful risk stratification is essential to determine which patients may benefit from early therapy. Mayo Clinic’s 20/20/20 risk model remains a widely used framework, with high-risk patients meeting at least two criteria: more than 20% bone marrow plasma cells, 2 or more grams of M protein, or a free light chain ratio of more than 20.
High-risk patients with smoldering disease face a roughly 46% risk of progression to active myeloma within 2 years, Dr. Abhyankar said. Trials, such as AQUILA, have explored daratumumab monotherapy in this population, demonstrating promising progression-free survival outcomes. While the approach is still somewhat controversial, early therapy may be considered for carefully selected patients, Dr. Abhyankar said.
Furthermore, she highlighted that cytogenetic risk and trends in disease markers over time are crucial when deciding whether to initiate therapy. Patients with high-risk cytogenetics and evolving biomarkers may be strong candidates for early treatment with daratumumab, whereas those with stable low-risk profiles may continue under active surveillance.