Multivariate predictive model for bone marrow sampling in MGUS patients

1. A multivariate predictive model was developed to help determine when a bone marrow sample would help distinguish between patients with monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM).

2. The model aimed to minimize unnecessary bone marrow sampling in this population. 

Evidence Rating Level: 2 (Good)

Study Rundown: MGUS may be a precursor to MM and other lymphoproliferative disorders. The way to distinguish between SMM and MGUS is by looking at the bone marrow plasma cells (BMPC). They are distinguished by 10% or higher BMPC, have a higher progression risk, and need management. SMM is the presence of BMPC between 10-59% or an M protein concentration of 30 g/L or higher but without a myeloma-defining event and is a middle stage between MGUS and MM. It is necessary to obtain a bone marrow sample to distinguish between people with MGUS and SMM. However, it requires extensive resources and may be painful to undergo. Since knowing when to obtain a bone marrow sample can be challenging, this study developed a multivariable predictive model to understand the chances of someone with MGUS having SMM or worse. A total of 75,422 individuals sent their blood samples to undergo serum protein electrophoresis and analysis. The participants who had abnormal screening results consistent with MGUS were then randomized into one of three groups. The study was limited as the prediction model used requires external validation. Overall, the established multivariate prediction model may be used to defer bone marrow sampling.

Click here to read the study in AIM

In-Depth [predictive model]: The goal of this cohort study was to predict how many individuals with MGUS also have SMM or worse and decide whether to obtain a bone marrow sample or not. Citizens of Iceland born in 1975 or earlier and alive on September 9, 2016, were asked to complete a blood sampling test to determine their eligibility in the study. Those included were individuals presumed to have MGUS, whereas the study excluded individuals with IgM MGUS since this type will not progress to MM.  Also excluded were those categorized as low-risk MGUS, those who never participated in bone marrow sampling, and individuals who did their bone sampling 365 days from the screening blood sample.  The median age of the participants was 68 years (interquartile range [IQR], 60 to 75 years), and 578 (55.4%) were men. Of the participants, 158 (15.1%) people had 10% or higher BMPC sampling and 2 (1.3%) had MM. The median predicted risk for SMM by bone marrow criteria was 7.7% (IQR, 4.3% to 17.4%). The risk for SMM or worse was only slightly higher for biclonal MGUS (odds ratio [OR], 1.64 [95% CI, 1.11 to 2.44]), IgA MGUS (OR, 1.48 [CI, 0.98 to 2.33]) and light-chain MGUS (OR, 1.04 [CI, 0.60 to 1.80]). The M protein concentration (OR between 3.9 g/L [75^th percentile] and 2.1 g/L [median], 2.07 [CI, 1.63 to 2.63 g/L]) and FLC ratio (OR between 1.9 [75^th percentile] and 1.2 [median], 1.29 [CI, 1.13 to 1.47]) were the greatest predictors of SMM or worse occurring. The c-statistic for the SMM prediction model was 0.85 (CI, 0.82 to 0.89). The predictive model helped determine whether individuals with MGUS should get bone marrow sampling or be referred to a hematologist.

Image: PD

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