International Kidney and Monoclonal research Group (IKMG) recommendations for screening for acute kidney injury (AKI) secondary to multiple myeloma (MM) include the assessment of patients with the serum free light chain test (sFLC). Here we compare the economic impact of following this recommendation compared to standard serum and urine electrophoretic techniques. An economic model was constructed using published UK data and centre specific clinician advice. The model compared the following scenarios: (i) serum protein electrophoresis (SPEP) + sFLC (IKMG recommendation), (ii) SPEP alone, (iii) SPEP + urine electrophoresis (SPEP + UPE), with a positive test in scenarios (i)—(iii) proceeding to immunofixation electrophoresis (IFE); (iv) all electrophoretic methods run in parallel (SPEP + UPE + sIFE + uIFE). The key economic drivers in the model were length of in-patient stay and dialysis costs. The incremental costs per QALY gained were modelled over a 365d time horizon. The economic model utilized a decision tree structure to the time of diagnosis and a Markov model including the health states: dialysis dependence, renal function recovery, other cause of AKI and death. The model structure and assumptions were validated through clinician consultation. Survival in the diagnostic pathway was estimated using hazard ratios applied to survival of MM based on the stage of AKI, obtained from a retrospective observational study (Han, et al., 2013). Survival within the Markov model post-diagnosis was based on UK data stratified for cast nephropathy patients who had or had not recovered renal function. Post-diagnosis, a probability of renal recovery based on the duration of AKI prior to diagnosis was applied. Utility values in the decision tree structure were estimated using the Modification of Diet in Renal Disease equation. The Markov model employed previously published utility values in MM with a decrement applied for dialysis dependence. Costs for medical resource use, medical management, dialysis, adverse events associated with dialysis and terminal care were derived from the 2012-2013 NHS Reference Cost and British National Formulary. Key user defined values for the comparison included a presenting patient distribution of 10% stage 2 AKI, 45% stage 3 AKI (dialysis independent) and 45% stage 3 AKI (dialysis dependent), 1% incidence of cast nephropathy as a cause of AKI, and a 20% incidence of renal biopsy following a positive diagnostic result. User amendable fields ensure the model is amenable to refinement as new data on assay performance and patient pathways become available. The incremental costs and QALYs for each comparator are shown in Table 1. The model predicts the pathway with SPEP + sFLC to be dominant; SPEP + sFLC accrues the most QALYs and the least costs. The savings in the diagnostic decision tree (£7, £31, -£5, respectively) are driven by reduced dialysis and in-patient bed stay costs. In the treatment pathway savings (£34, £37, £41, respectively) are driven by reduced dialysis costs. Probabilistic sensitivity analysis showed the model results to be robust - the probability of SPEP + sFLC being cost-effective at a £20,000 per QALY willingness to pay threshold was 98.6%, 93.8%, 92.6%, respectively. Table 1 - Base Case Cost-Effectiveness Results Model Results SPEP + sFLC SPEP Difference Total Cost (GBP) £427 £467 -£40 Total QALYs 0.6245 0.6235 0.00099 ICER=Incremental Cost/ Incremental QALY Dominant Model Results SPEP + sFLC SPEP Difference Total Cost (GBP) £427 £495 -£68 Total QALYs 0.6245 0.6231 0.00133 ICER=Incremental Cost/ Incremental QALY Dominant Model Results SPEP + sFLC SPEP Difference Total Cost (GBP) £427 £463 -£36 Total QALYs 0.6245 0.6239 0.00055 ICER=Incremental Cost/ Incremental QALY Dominant This model supports the recommended international guidelines for screening for AKI secondary to MM. Inclusion of the sFLC assay improves the probability of renal recovery and survival by reducing time to diagnosis and treatment. Cost savings and QALY gains are found in both the diagnostic stage and treatment stage of the patient pathway. The SPEP + sFLC pathway is therefore cost-effective at a willingness to pay threshold of £20,000 per QALY with a high probability of cost-effectiveness against all comparator pathways from probabilistic sensitivity analysis. The model template may be used in future health economic models to assess the contribution of new assays into diagnostic algorithms. Disclosures No relevant conflicts of interest to declare.

Monoclonal gammopathy of undetermined significance (MGUS) has a 1% overall risk of progression to symptomatic disease per year. Previously, monoclonal Ig (M-protein) isotype (IgA or IgM) and concentration (≥10g/L) have been used to risk stratify patients. In 2005, Rajkumar et al. reported on three independent risk factors: M-protein concentration ≥15g/L, M-protein isotype IgA or IgM, and an abnormal free light chain ratio (FLCr). An abnormal FLCr, determined by polyclonal antibody-based nephelometric analysis, had a 7.4 fold relative risk for MGUS progression in the absence of the other two factors. The International Myeloma Working Group (IMWG) recommends inclusion of all three factors for MGUS risk stratification, with low risk patients being referred to primary care while, intermediate and higher risk patients have bone marrow biopsies and skeletal surveys at presentation and are then followed annually by a haematologist. Here, we compare costs and resource use associated with the IMWG recommendations with the previous risk stratification approach. The model consists of a decision tree structure from incidental finding of an M-protein level <30g/L to risk stratification, followed by a Markov structure comprising health states for non-stratified, low risk and ≥1 risk factor MGUS, smouldering multiple myeloma, symptomatic disease and death. The distribution of patients in the health states was based on incidence data and the proportion of patients in each risk strata in a US cohort, published by Rajkumar et al. (2005). The proportion of patients stratified as low risk in the previous approach was 33% compared with 39% when following IMWG recommendations. Patients with MGUS experience higher mortality relative to age- and sex-matched healthy individuals; survival was therefore estimated by applying a relative risk of death to general population life tables (Office for National Statistics, 2014). Risk of progression to symptomatic disease was obtained by fitting exponential curves to the published data of Rajkumar et al. (2005) and Kyle et al. (2002) from the Mayo Clinic. Costs of laboratory tests and resources were derived from the 2013-14 NHS and PSSRU 2014 data. Resource use was based on IMWG guidelines and clinician advice. The model used a 5-year time horizon, with outcomes discounted at an annual rate of 3.5%. The model predicts that following IMWG recommendations results in lower costs, fewer bone marrow biopsies, skeletal surveys and haematologist consultations, and more referrals to primary care (Table 1). The pathway following IMWG recommendations increases referrals to primary care; however, the model shows, at Year 5, only 1.5% of those in primary care are predicted to progress to symptomatic disease compared to 3% of those in the previous risk stratification pathway. Cost savings in the diagnostic pathway were driven by fewer skeletal surveys and bone marrow biopsies: -₤13.75 and -₤19.90 per patient, respectively. In the Markov model, savings were driven by the reduction in haematologist consultations, -₤85.91 per patient. One-way sensitivity and scenario analyses indicated that results remained stable unless the proportion of patients referred to primary care in the IMWG pathway was ≤32% or the proportion of patients referred back to primary care in the previous risk stratification approach was ≥39%. Probabilistic sensitivity analysis, based on 10,000 probabilistic simulations, showed that the IMWG recommendations have a 92.5%, 95.4%, 95.4% and 92.1% probability of reducing costs, bone marrow biopsies, skeletal surveys and haematology consultations, respectively, and a 95.4% probability of more patients being referred back to primary care. The UK incidence of newly identified MGUS cases is estimated to be >7000 per year. Applying the IMWG recommendations, including FLCr analysis, therefore leads to substantial cost savings and reduced resource use in both the diagnostic and long-term pathways. Benefits to patients include fewer required bone marrow biopsies and skeletal surveys, while fewer patients identified as low risk are predicted to progress to symptomatic disease. As practice moves towards a more systematic out-of-hospital approach, further benefits are anticipated for the management of patients with MGUS. Haematology clinic resources can then be allocated to other conditions, while maintaining confidence that all MGUS patients are appropriately managed. Disclosures Pratt: The Binding Site Group Ltd: Other: Member of Medical Advisory Board. Harding:The Binding Site Group Ltd: Employment, Membership on an entity's Board of Directors or advisory committees. Powner:The Binding Site Group Ltd: Employment. Hughes:The Binding Site Group Ltd: Employment. Cook:The Binding Site Group Ltd: Other: Member of Medical Advisory Board.