Dr Krishnan on the Complexity of Developing a Consensus for Risk Stratification in Smoldering Myeloma

"Smoldering myeloma is a very challenging area. [With] risk stratification, there are multiple [models], so it's hard to get a true consensus. I think we all agree on the [principle] that certain features confer higher risk, [such as] cytogenetics [and] disease burden. I think the [main point] we agree on as a consensus is [using] those models to help guide [the] decision [of] whether to treat or not, meaning that most of us, when we think about treating smoldering [myeloma], really think about [it] in the context of high-risk smoldering disease."

Amrita Krishnan, MD, professor, Department of Hematology & Hematopoietic Cell Transplantation; director, the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope; executive medical director, Hematology, City of Hope Orange County, discusses the complexities of risk stratification in smoldering multiple myeloma and the need for a clinical consensus to guide treatment decisions. Given the heterogeneity of the disease and the variability in risk models, establishing a standardized approach remains a challenge, she explains.

Risk stratification in smoldering multiple myeloma is critical for distinguishing patients who may progress to symptomatic multiple myeloma from those who can be safely monitored. However, Krishnan notes that multiple risk stratification models exist that each incorporate different criteria, such as cytogenetics, disease burden, and biomarkers. Despite the variability among these models, consensus exists that certain features, such as high-risk cytogenetics and greater tumor burden, are strongly associated with an increased likelihood of disease progression.

A key area of agreement within the field is the role of risk stratification in guiding treatment decisions. Krishnan emphasizes that treatment in smoldering multiple myeloma is primarily considered in the context of high-risk disease. While some patients with standard-risk smoldering multiple myeloma may never progress to symptomatic myeloma, those classified as high-risk face a significantly increased likelihood of progression within two years. For these patients, early intervention strategies, such as lenalidomide (Revlimid)-based therapy or clinical trial enrollment, may be appropriate. However, the challenge lies in achieving a consensus on which specific patients should receive early treatment vs those who should be observed.

Further refinement of risk models remains necessary to improve stratification accuracy and treatment decision-making, she says. The integration of next-generation sequencing and minimal residual disease assessment may enhance predictive capabilities, allowing for a more individualized approach. Additionally, the role of novel biomarkers in refining risk assessment continues to be an area of active investigation.

Krishnan underscores the need for expert consensus in translating risk models into clinical practice. While current models provide a framework, real-world applicability requires standardization to ensure consistent decision-making. Consensus guidelines help streamline patient selection for early treatment, optimize monitoring strategies, and ultimately improve patient outcomes.