Abstract
Introduction In 2014, the International Myeloma Working Group (IMWG) modified the diagnostic criteria for active multiple myeloma (MM) to include three additional MM defining events, often referred to as SLiM criteria: S – ≥60% bone marrow plasma cells (BMPC), Li – a serum free light chain (FLC) ratio ≥100, and M – >1 focal lesion on magnetic resonance imaging (MRI). The SLiM criteria are used to identify patients who do not yet have “CRAB” symptoms (Calcium elevation, Renal dysfunction, Anemia, and Bone lesions) but may benefit from early intervention. This study examined the clinical features of patients at the initiation of MM treatment; moreover, we evaluated whether patients who met only SLiM criteria were more likely to initiate treatment after the implementation of the SLiM-CRAB criteria in 2014.
Methods We conducted a retrospective cohort study using data from the nationwide US Veterans Health Administration (VHA), 2005-2024. MM patients were defined as patients receiving any of the following MM specific treatments, including bortezomib, carfilzomib, lenalidomide, or daratumumab. The SLiM-CRAB features of these patients within one year prior to the initiation of any MM treatment (in addition to the aforementioned four treatments) were also extracted. Each feature was defined as follows: S – ≥60% BMPC; Li – a FLC involved-to-uninvolved ratio ≥100; M – focal lesion identified from MRI reports; C – serum calcium concentration greater than 11 mg/dL; R – estimated Glomerular Filtration Rate (eGFR) less than 44 mL/min/1.73 m2; A – hemoglobin (Hb) levels below 10 g/dL; and B – bone lesion identified by X-ray, CT, or PET-CT imaging. Clinical features of patients at the time of MM treatment were characterized, with a particular focus on the proportion of SLiM-only cases.
Time from the date of protein electrophoresis result indicating monoclonal gammopathy of undetermined significance (MGUS), to the date of first MM treatment was assessed using the Cox proportional hazards models to compare the treatment pattern for MGUS patients diagnosed in 2005-2014 against those diagnosed in 2015-2024.
All tests are two sided, and statistical significance was set at P <.05. Statistical analyses were conducted using STATA 18 version SE.
Results A total of 15,754 patients received targeted MM treatments in the VHA between 2005 and 2024. The average age at treatment initiation was 70.1 (SD: 9.6) years, with 97% of patients being male and 63% white.
Comparing the periods of 2005–2014 and 2015–2024, the proportion of patients presenting with ≥60% BMPC at MM treatment increased from 21.1% to 29.1% (p<0.001). The percentage of patients with a serum FLC ratio ≥100 increased from 20.1% to 22.1% (p<0.05). The proportion with more than one focal lesion on MRI from 12.8% to 11.5% (p<0.05). For CRAB-defining features, hypercalcemia decreased from 12.7% to 9.5% (p<0.001), renal impairment from 41.4% to 36.8% (p<0.001), anemia from 44.8% to 39.3% (p<0.001), and bone lesions on X-ray, CT, or PET-CT from 48.2% to 40.7% (p<0.001). The proportion of patients with SLiM-only at treatment initiation increased from 3.6% in 2005–2014 to 6.0% in 2015–2024 (p<0.001). Despite this increase, most patients initiating MM treatment continued to present with at least one CRAB feature.
Patients diagnosed with MGUS in 2015-2024 were more likely to initiate treatment (HR = 1.61; 95% CI: 1.52–1.71). At 3 years, the cumulative incidence of MM treatment was 21.9% (95% CI: 21.0%–22.8%) for patients diagnosed with MGUS in 2005–2014, compared to 33.8% (95% CI: 32.6%–35.0%) for those diagnosed in 2015–2024 (p<0.001). Among patients who received MM treatment with a prior MGUS diagnosis (n=6,706), the average time from MGUS diagnosis to MM treatment was 2.8 (median: 1.1) years for patients diagnosed in 2005–2014, compared to 1.0 (median: 0.2) year for those diagnosed in 2015–2024.
Conclusions In this large, national VHA cohort, the clinical presentation of patients receiving MM treatment has evolved over time from 2005-2024. There was an increase in patients initiating treatment based on SLiM-only features, accompanied by a decline in CRAB-defining organ damage at treatment initiation. Patients diagnosed with MGUS after 2014 were more likely to initiate MM treatment. These findings underscore a paradigm shift in MM management within the VHA toward earlier diagnosis and treatment following the SLiM-CRAB criteria updates in 2014.
