From criteria to clinic: How updated SLiM CRAB criteria influence multiple myeloma diagnostic activity.
Authors: Ji Mengmeng , Wang Mei , Shih Yi-Hsuan , Huber John , Fiala Mark Aaron , Wang Rong , Sanfilippo Kristen Marie , Thomas Theodore Seth , Wang Shi-Yi , Schoen Martin W. , Chang Su-Hsin 
Published: June 2024

7556 Background: Multiple myeloma (MM) is a plasma cell malignancy, which is preceded by asymptomatic, precursor state of monoclonal gammopathy of undetermined significance (MGUS). Once diagnosed with MGUS, monitoring for progression to MM is recommended. The diagnostic criteria for active MM include presence of ≥1 CRAB features (hypercalcemia, renal failure, anemia, or one or more osteolytic bone lesions on skeletal radiology, CT or PET/CT imaging) in addition to clonal plasma cells on bone marrow. In 2014, the International Myeloma Working Group (IMWG) added SLiM to the criteria: clonal bone marrow plasma cells ≥60%, serum free light chain (FLC) ratio ≥100, and >1 focal lesion on magnetic resonance imaging (MRI). This study investigated the longitudinal influence of the updated diagnostic criteria on the utilization of imaging examination and the number of MM diagnoses overtime among patients with MGUS. Methods: We used data from the U.S. Veterans Health Administration (VHA) 2010-18. Patients with MGUS were identified by a published natural language processing (NLP) model. MM cases diagnosed under the old criteria were identified using International Classification of Diseases (ICD)-9/10 codes for CRAB symptoms, while cases diagnosed under the new criteria were identified using a published NLP-assisted model developed based on the SLiM-CRAB criteria. We then performed a counterfactual comparison to contrast the number of MM cases that would have been diagnosed under the old criteria with those under the new criteria. To monitor changes in the use of advanced imaging technology, we calculated the frequency of imaging examinations orders <1 year following MGUS diagnosis, including whole-body/spine computed tomography (CT), MRI and positron emission tomography-CT. Results: A total of 29,336 MGUS patients were identified. MGUS patients undergoing whole-body or spine MRI/CT scans <1 year following-MGUS diagnosis increased from 15.72% during 2010-13 to 21.06% during 2015-18 ( P = 0.002). In 2010-13, 346 MM cases were diagnosed per year on average with the old criteria. This number increased to 666 cases in 2015-18 with the updated criteria. Had the new criteria been applied retrospectively to 2010-13, the number of diagnoses would have increased 28% (to 441 cases per year). Conversely, had the old criteria been applied to 2015-18, the number of diagnoses would have decreased by 29% (to 473 cases per year). Conclusions: Our study revealed a significant increase in MM diagnoses after adding the SLiM biomarkers into the updated diagnostic criteria. In parallel, there has been an increase in the use of CT/MRI imaging for MGUS patients, suggesting a shift towards more aggressive diagnostic strategies. Further analysis is warranted to evaluate the positive detection rate of active MM through imaging and to understand the implications of early detection on MM patient outcomes.