Identifying High-Risk Smoldering Multiple Myeloma for Early Intervention

Area of Science:

• Hematology
• Oncology
• Clinical Research

Background:

• Smoldering multiple myeloma (SMM) is a precursor to active multiple myeloma, and early treatment may benefit high-risk patients.
• Inconsistent definitions for high-risk SMM can lead to the inclusion of different disease subsets, complicating treatment decisions.

Purpose of the Study:

• To compare the AQUILA trial inclusion criteria and the 2/20/20 risk stratification model for identifying high-risk SMM.
• To assess the progression risk associated with each definition in distinct SMM cohorts.

Main Methods:

• A cohort study utilizing data from the population-based Iceland Screens, Treats, and Prevents Multiple Myeloma (iStopMM) study and the Danish Lymphoid Cancer Resource (DALY-CARE) clinical database.
• Retrospective analysis of progression risk based on initiation of treatment for individuals meeting high-risk criteria under both the AQUILA and 2/20/20 models.

Main Results:

• The AQUILA criteria identified a higher proportion of high-risk SMM (34% in iStopMM, 55% in DALY-CARE) compared to the 2/20/20 model (8% in iStopMM, 19% in DALY-CARE).
• Individuals classified as high-risk by the AQUILA criteria in the clinical cohort showed a 2-year progression risk of 27.0% (14.5% annual rate).
• In contrast, those defined as high-risk by the 2/20/20 model exhibited a higher 2-year progression risk of 44.1% (27.3% annual rate).

Conclusions:

• The 2/20/20 model more accurately identifies a high-risk SMM subgroup with a substantially higher progression risk compared to the AQUILA criteria.
• These findings suggest that the 2/20/20 model is more suitable for selecting patients with SMM who are most likely to benefit from early therapeutic intervention.