In a study reported as a research letter in JAMA Oncology, Hill et al found a low degree of concordance in risk categorization among commonly used smoldering multiple myeloma risk models.

Study Details

The study involved application of the Mayo Clinic Risk Stratification Model 2008, the Programa para el Tratamiento de Hemopatias Malignas (PETHEMA) model, and the Mayo Clinic Risk Stratification Model 2018 to data from a total of 145 patients enrolled in two National Cancer Institute–sponsored clinical trials between April 2010 and June 2020.

Patients had risk scores assigned from each model and were categorized as low-risk, intermediate-risk, or high-risk based on each model.

Key Findings

Among the 145 patients, 42 (29.0%) had agreement in risk stratification across low-, intermediate-, and high-risk categories between the MAYO 2008 and PETHEMA models, and 72 (49.7%) had agreement across risk categories between the MAYO 2018 and PETEMA models. A total of 24 patients (16.6%) had agreement in risk stratification across all three models.

Numbers of patients categorized as low-, intermediate-, and high-risk were: 60, 76 (total non–high-risk = 136), and 9 on the MAYO 2008 model; 40, 40 (total non–high-risk = 80), and 65 on the MAYO 2018 model; and 21, 46 (total non–high-risk = 67), and 78 on the PETHEMA model. P values were < .001 for discordance across all risk categories and < .001 for discordance between non–high-risk vs high-risk across all three risk models.

As discussed by the investigators, “The accurate identification of patients with smoldering multiple myeloma at highest risk of developing multiple myeloma remains difficult. While the 2018 Mayo Clinic model has a higher concordance rate with the PETHEMA model, it remains significantly discordant. Furthermore, these models are limited because they do not incorporate sensitive imaging techniques, such as positron emission tomography–integrated computed tomography, which can aid in risk stratifying patients who are at highest risk of developing symptomatic multiple myeloma…These results suggest that the current clinical variables used to determine risk are not reliable, most likely because they are markers of disease burden, subject to increase over time, and not true markers of biological disease characteristics.”

They concluded “…The incorporation of genomic signatures has the potential to significantly improve smoldering multiple myeloma risk stratification and is urgently needed. Until that time, it remains unclear which patients warrant early intervention, and we would caution against treatment of patients with smoldering multiple myeloma outside of a clinical trial.”

Dickran Kazandjian, MD, of the Multiple Myeloma Program, Center for Cancer Research, National Cancer Institute, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by the National Institutes of Health Intramural Research Program and a grant from the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.