Introduction

In 2014, the International Myeloma Working Group (IMWG) modified the diagnostic criteria for active multiple myeloma (MM) to include three additional myeloma defining events, often referred to as SLiM criteria: S for ≥sixty percent bone marrow plasma cells, Li for a serum free light chain (FLC) ratio ≥100, and M for >1 magnetic resonance imaging (MRI)-defined focal lesion. Little is known about the utilization of the new criteria and the diagnostic tests to detect SLiM-defining events. To address this gap, we evaluated the use of SLiM-defining diagnostic tests including bone marrow biopsy (BMBX), FLC ratio testing, and MRI scan, in patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS).

Methods

We conducted a retrospective cohort study in the nationwide US Veterans Health Administration (VHA) from 2005-2024. Patients with a serum protein electrophoresis (SPEP) indicating abnormal monoclonal protein (M-protein) levels <3 g/dL were considered as having MGUS. The date of the SPEP was defined as the MGUS diagnosis date. The utilization of BMBX, FLC ratio testing, and MRI scan was identified using Current Procedural Terminology and International Classification of Diseases Procedure codes. Test outcomes were extracted from laboratory results, radiology reports, and pathology reports using natural language processing techniques.

The percentage of MGUS patients receiving SLiM-defining tests within 1 year following MGUS diagnosis was compared during the CRAB criteria period (2005-2014) with the SLiM-CRAB criteria period (2015-2024). Differences between time periods were assessed using Chi-square tests for categorical variables and t-tests for continuous variables. Statistical analyses were conducted using STATA 18 version SE and significance was set at P <.05.

Results

The cohort included 15,412 patients with MGUS. The average age at diagnosis was 70.4 years (SD: 10.1). Among patients with MGUS, the proportion of patients receiving FLC ratio testing within 1 year of diagnosis increased from 38.2% in 2005-2014 to 80.2% in 2015-2024 (P <.001); BMBX increased from 31.5% to 37.9% (P <.001); MRI scan from 19.3% to 24.2% (P <.001).

The plasma-cell percentage of first BMBX after MGUS is significantly higher in 2015-2024 compared with 2005-2014 (29.6% vs 26.0%, p<.001). The average serum FLC ratios at first BMBX (65.2 vs 135.7; P < 05) and M-protein levels at first BMBX (0.9 vs 1.2; P <.001) were significantly lower in 2015-2024 compared with 2005-2014.

Conclusion

Our findings show a significant increase in the utilization of SLiM-defining diagnostic tests following the introduction of new MM diagnostic criteria in 2014. Patients diagnosed with MGUS were referred to BMBX at an earlier stage. The rise in diagnostic testing among patients diagnosed with MGUS may promote earlier diagnosis of MM for timely management of the disease progression but could also lead to patient anxiety and healthcare overutilization. Future studies are needed to assess long-term clinical outcomes and the cost-effectiveness of the SLiM-CRAB diagnostic criteria versus the CRAB criteria or early diagnostic approaches in general.

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2025
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