iStopMM Risk Score Helps Predict Which MGUS Patients Need Bone Marrow Biopsy
CLINICAL QUESTION: Does my patient with a monoclonal protein and probable monoclonal gammopathy of undetermined significance (MGUS) need a bone marrow biopsy to rule out smoldering multiple myeloma (SMM)?
BACKGROUND: MGUS is found in 4.2% of adults over the age of 50. Overall rates of progression to multiple myeloma (MM) are low (0.5% to 1% per year), with most never progressing. Only bone marrow biopsy (BMbx) can tell SMM bone marrow plasma cells (BMPC) (10% to 59%) from MGUS (BMPC less than 10%).
STUDY DESIGN: Observational cohort study
SETTING: A sub-study within the iStopMM (Iceland Screens, Treats, or Prevents Multiple Myeloma) MM screening study SYNOPSIS: Within the iStopMM study, the data for a cohort of 1,043 persons with monoclonal gammopathy on blood testing were used to develop a statistical model. All had undergone BMbx, which showed 880 had MGUS, 158 had SMM, and two had MM. The model predicts risk of “SMM or worse” on BMbx. The iStopMM model outperformed the Mayo Clinic risk prediction model. The concordance statistic was 0.85 versus 0.67. If a risk threshold of SMM below 10% was selected, then 58.8% would be spared BMbx, only missing 3.6% who had SMM. With the Mayo Clinic model, you would spare only 37% BMbx and miss 6.2% who had SMM. Limitations include: a screening population (not hospitalized patients), a largely white and genetically homogeneous population, the need for external validation, and a lack of outcomes studies. This model outputs risk of “SMM or worse” as opposed to risk categories. This allows shared decision making based on individual risktolerance. This model should not be applied if patients have signs or symptoms of gammopathy complications, such as bone pain, fatigue, bleeding, lymphadenopathy, B symptoms, amyloid symptoms, or proteinuria.
BOTTOM LINE: If your patient with a monoclonal gammopathy has an iStopMM risk score less than 10%, they can safely forego a bone marrow biopsy.
CITATION: Eythorsson E, et al. Development of a multivariable model to predict the need for bone marrow sampling in persons with monoclonal gammopathy of undetermined significance : a cohort study nested in a clinical trial. Ann Intern Med. 2024;177(4):449-457. doi: 10.7326/M23-2540.
Dr. Stafford
Dr. Stafford is a hospitalist in the department of medicine at Duke Regional Hospital and an assistant professor of medicine at Duke University in Durham, N.C.