The Impact of Alternate Methodological and Structural Assumptions on Results of Cost-effectiveness Analysis: Empirical Evidence using Three Indian Economic Evaluations.

BACKGROUND: Despite advancement in methods and application of economic evaluations (EEs), there are several uncertainties. OBJECTIVES: To assess the impact of alternate methodological and structural assumptions for four key principles of EE, on the results of cost-effectiveness analysis. MATERIALS AND METHODS: Three previously published model-based EEs were used: (1) Integrated Management of Neonatal and Childhood Illnesses (IMNCIs) intervention; (2) intervention for multiple myeloma, and (3) safety-engineered syringes (SES) intervention. A series of empirical analyses was undertaken to assess the impact of alternate assumptions for discount-rate, time-horizon, study perspective, and health outcome measure, on incremental cost-effectiveness ratio (ICER), and interpretation of cost-effectiveness. RESULTS: Increasing discount rate resulted in an increase in ICERs, for all three case-studies; however, there was no change in the conclusions. Using shorter time-horizons resulted in a significant increase in ICERs, the multiple myeloma intervention remained cost-ineffective, SES intervention became cost-ineffective, whereas IMNCI intervention remained cost-effective, despite a three-fold increase in ICER. On using disability adjusted life years instead of quality adjusted life years, ICERs increased to 0.04, 2 and 4 times for SES, IMNCI and multiple myeloma interventions, respectively. On analyzing results from a societal perspective, a decline in ICERs was observed. The decline was significant for IMNCI where the intervention turned dominant/cost-saving. In the other two case-studies decline in ICERs was modest, 32% for multiple myeloma, and 4% for SES. CONCLUSION: We observed a significant impact of using alternate assumptions on ICERs which can potentially impact resource-allocation decisions. Our findings provide strong argument in favor of standardization of processes and development of country-specific guidelines for conduct of EE.

Clinical and economic burden of medicare beneficiaries with multiple myeloma and renal impairment: An observational study.

Evidence on real-world clinical and economic outcomes in patients with multiple myeloma (MM) and renal impairment (RI) is limited in the United States. This retrospective study aimed to generate an updated comprehensive assessment of the clinical and economic outcomes of MM patients with RI using the Medicare research identifiable files data with Part D linkage, which might assist in assessing the total clinical and socioeconomic burden of these high-risk and challenging-to-treat patients. Treatment patterns and clinical and economic outcomes in first line (1L) to fourth line (4L) therapy were described in Medicare beneficiaries (2012 to 2018) for MM patients with RI (RI MM cohort). For reference purposes, information on a general cohort of MM patients was generated and reported to highlight the clinical and economic burden of RI. Since the goal was to describe the burden of these patients, this study was not designed as a comparison between the 2 cohorts. Compared with the general MM cohort (n = 13,573), RI MM patients (24.9%) presented high MM-associated comorbidities. In the RI MM cohort, bortezomib-dexamethasone (45.7%), bortezomib-lenalidomide (18.6%), lenalidomide (12.3%), and bortezomib-cyclophosphamide (12.1%) were the most prevalent regimens in 1L; carfilzomib and pomalidomide were mostly received in 3L to 4L; and daratumumab in 4L. Across 1L to 4L, the RI MM cohort presented shorter median real-world progression-free survival (1L: 12.9 and 16.4 months) and overall survival (1L: 31.1 and 46.8 months) and higher all-cause healthcare resource utilization (1L incidence rate of inpatient days: 12.1 and 7.8 per person per year) than the general MM cohort. In the RI MM cohort, the mean all-cause total cost increased from 1L to 4L ($14,549-$18,667 per person per month) and was higher than that of the general MM cohort. RI MM patients presented higher clinical and economic burdens across 1L to 4L than the general MM patients in real-world clinical practice.

Mixed-Methods Study on the Responsiveness of the Comprehensive Score for Financial Toxicity Among People With Multiple Myeloma.

PURPOSE: Financial toxicity is a contributor to the psychosocial burden of cancer care. There is no consensus measure of financial toxicity; however, recent studies have adopted the Comprehensive Score for Financial Toxicity (COST). Despite its growing popularity, data on the responsiveness to change of the COST instrument are lacking. To address this gap in the literature, we performed a sequential mixed-methods study of people with multiple myeloma. MATERIALS AND METHODS: In the quantitative phase of the study, we collected COST scores at two time points approximately 8 weeks apart from 72 patients. In the qualitative phase, we conducted semistructured interviews with a subset of 12 patients who reported the largest changes in scores. The qualitative data were analyzed using a deductive coding scheme developed using the Framework Method in the context of a commonly cited conceptual model of financial toxicity. RESULTS: The median absolute change in COST scores was four points (IQR, 2-6). Only 13% of the sample had the same COST scores at both assessments; 38% had an improved score and 50% had a worsened score. Only, seven of the 12 patients (58%) interviewed reported changes to one or more of the constructs in the conceptual model of financial toxicity. Most commonly, changes to out-of-pocket medical costs were reported (5/12). Changes to nonmedical expenses (n = 2) and subjective financial distress without changes to objective financial burden (n = 2) were also reported. CONCLUSION: Additional research is needed to explicate changes in COST scores over time.

The cost of multiple myeloma and its complications: A single-center study from Oran, Algeria.

BACKGROUND: The expenses of multiple myeloma (MM) represent a real economic and societal burden for patients and health authorities. However, very little is known about the situation in Algeria. Therefore, the aim of this study is to evaluate the costs generated by the management of MM and its complications in Algerian patients. MATERIALS AND METHODS: An observational retrospective study conducted on patients diagnosed with MM, from January 1st, 2019 to April 31st, 2023, at the Establishment Hospitalier Universitaire November 1st, Oran. A bottom-up costing methodology was used to assess the phase-specific cost and the complication burden. RESULTS: In total, 249 qualified for the study. For autologous stem cell transplantation (ASCT) eligible patients, the mean per patient cost of treating myeloma was estimated at: induction regimen ($4072); ASCT ($2899); consolidation ($1538); and maintenance ($355.76). The mean drug cost for ASCT-ineligible patients was $1421. The use of generic bortezomib and generic melphalan has led to a reduction in expenses of $1,075,181 ($5,024 per patient; 55.35%) and $10,864 ($487 per patient; 15.07%), respectively. Another cost-saving adaptation was ASCT using non-cryopreserved (NC) stem cells. The cost of managing MM complications was $177,782 per year. CONCLUSION: A number of adjustments have been implemented to the management of MM over time to improve clinical efficacy and reduce costs in Algeria. However, this may have come with a startlingly high cost of complications.

Bone Marrow Biopsies: Is CT, Fluoroscopy, or no Imaging Guidance the Most Cost-Effective Strategy?

RATIONALE AND OBJECTIVES: To determine the most cost-effective strategy for pelvic bone marrow biopsies. MATERIALS AND METHODS: A decision analytic model from the health care system perspective for patients with high clinical concern for multiple myeloma (MM) was used to evaluate the incremental cost-effectiveness of three bone marrow core biopsy techniques: computed tomography (CT) guided, and fluoroscopy guided, no-imaging (landmark-based). Model input data on utilities, costs, and probabilities were obtained from comprehensive literature review and expert opinion. Costs were estimated in 2023 U.S. dollars. Primary effectiveness outcome was quality adjusted life years (QALY). Willingness to pay threshold was $100,000 per QALY gained. RESULTS: No-imaging based biopsy was the most cost-effective strategy as it had the highest net monetary benefit ($4218) and lowest overall cost ($92.17). Fluoroscopy guided was excluded secondary to extended dominance. CT guided biopsies were less preferred as it had an incremental cost-effectiveness ratio ($334,043) greater than the willingness to pay threshold. Probabilistic sensitivity analysis found non-imaging based biopsy to be the most cost-effective in 100% of simulations and at all willingness to pay thresholds up to $200,000. CONCLUSION: No-imaging based biopsy appears to be the most cost-effective strategy for bone marrow core biopsy in patients suspected of MM. CLINICAL RELEVANCE: No imaging guidance is the preferred strategy, although image-guidance may be required for challenging anatomy. CT image interpretation may be helpful for planning biopsies. Establishing a non-imaging guided biopsy service with greater patient anxiety and pain support may be warranted.

Budget Impact Analysis of Idecabtagene Vicleucel for the Treatment of Adult Patients with Relapsed or Refractory Multiple Myeloma in the US.

BACKGROUND: Gene therapy is known to be unaffordable to those who need it the most; however, evidence on the financial impact is limited. OBJECTIVE: This study aimed to estimate the budget impact and affordability of the gene therapy idecabtagene vicleucel for the treatment of adult patients with relapsed or refractory multiple myeloma (rrMM) in the US over a 3-year period from the payer healthcare perspective. METHOD: A budget impact model was developed to estimate the budget impact to the US healthcare plan compared with bortezomib-based maintenance therapy. The target population size was based on a hypothetical 1-million-member plan over a 3-year time horizon with and without idecabtagene vicleucel adoption. The cost of drug acquisition, drug administration, and grade 3-4 adverse events (AEs) were calculated for both scenarios. The budget impact of idecabtagene vicleucel was calculated as the difference in costs for these two scenarios. Costs were extracted from IBM-Micromedex Red Book, Centers for Medicare and Medicaid Services, and the literature. A one-way sensitivity analysis was performed to ensure robustness. RESULTS: An estimated 22 patients with rrMM each year would be eligible for idecabtagene vicleucel. The model projected the annual cost per patient in the first year as $19,449 and $517,528.13 for bortezomib and idecabtagene vicleucel, respectively. Introducing idecabtagene vicleucel was predicted to increase the total budget by $13.4, $13.6, and $14 million in the first, second, and third years. There would be an additional $1.1128, $1.1252, and $1.1486 per member per month (PMPM) when using idecabtagene vicleucel over bortezomib. CONCLUSION: This study suggests that the high cost of the gene therapy idecabtagene vicleucel is justifiable due to the low number of rrMM patients.

Do patients with haematological malignancies suffer financial burden? A cross-sectional study of patients seeking care through a publicly funded healthcare system.

BACKGROUND: It is increasingly appreciated that some patients with cancer will experience financial burden due to their disease but little is known specifically about patients with haematological malignancies. Therefore, this study aimed to measure financial toxicity experienced by patients with haematological malignancies in the context of a publicly funded health care system. METHOD: All current patients diagnosed with leukaemia, lymphoma or multiple myeloma, from two major metropolitan health services in Melbourne, Australia were invited to complete a survey capturing; patient demographics, employment status, income sources, financial coping and insurances, OOP expenses and self-reported financial toxicity using a validated measure. RESULTS: Of the 240 people approached, 113 (47 %) participated and most had leukaemia (62 %). Forty-seven (42 %) participants experienced some degree of financial toxicity using the Comprehensive Score for financial toxicity (COST) instrument. On multivariate linear regression, older age (>65 years, p = 0.007), higher monthly income (>$8000, p = 0.008), not having and being forced into unemployment or early retirement (p < 0.001) remained significantly associated with less financial toxicity. CONCLUSION: Financial toxicity is present in Australian haematology patients and those at higher risk may be patients of working age, those without private health insurance and patients that have been forced to retire early or have become unemployed due to their diagnosis.

Efficacy and cost of G-CSF derivatives for prophylaxis of febrile neutropenia in lymphoma and multiple myeloma patients underwent autologous hematopoietic stem cell transplantation.

OBJECTIVES: To compare the efficacies and costs between pegfilgrastim and filgrastim prophylaxis for FN post-ASCT for lymphoma and multiple myeloma patients. METHODS: 43 patients who received pegfilgrastim (6 mg) were compared to a retrospective cohort of 129 patients that had received filgrastim post-ASCT. Hematopoietic recovery time, FN incidence and treatment costs were assessed and compared. RESULTS: The mean time to absolute neutrophil count engraftment was 8.72 ± 2.38 days for the prospective pegfilgrastim group and 9.87 ± 3.13 days for the retrospective filgrastim group (P = 0.027). The incidence of FN was 18.60% and 50.39% in prospective pegfilgrastim and retrospective filgrastim groups, respectively (P = 0.000). The mean cost of filgrastim was $617.22 ± 37.87, compared with $525.78 for pegfilgrastim (P = 0.032). DISCUSSION: Convenience, effectiveness, and safety of prophylaxis for FN in the prospective pegfilgrastim group were significantly improved compared to the retrospective filgrastim group in ASCT patients. CONCLUSION: Pegfilgrastim prophylaxis was more effective and convenient than filgrastim for FN prophylaxis in patients post-ASCT, especially for MM patients.

The high cost burden of third- to fifth-line treatments for multiple myeloma: unsustainable and unaffordable.

DISCLOSURES: No funding was provided for the writing of this commentary. In this commentary, the author refers to CivicaRx, for which Mayo Clinic is a founding member. As an employee of Mayo Clinic, the author does not have any direct financial relationship with or support from CivicaRx.

Phase-Specific and Lifetime Costs of Multiple Myeloma Among Older Adults in the US.

Importance: Health care costs associated with diagnosis and care among older adults with multiple myeloma (MM) are substantial, with cost of care and the factors involved differing across various phases of the disease care continuum, yet little is known about cost of care attributable to MM from a Medicare perspective. Objective: To estimate incremental phase-specific and lifetime costs and cost drivers among older adults with MM enrolled in fee-for-service Medicare. Design, Setting, and Participants: A retrospective cohort study was conducted using population-based registry data from the 2007-2015 Surveillance, Epidemiology, and End Results database linked with 2006-2016 Medicare administrative claims data. Data analysis included 4533 patients with newly diagnosed MM and 4533 matched noncancer Medicare beneficiaries from a 5% sample of Medicare to assess incremental MM lifetime and phase-specific costs (prediagnosis, initial care, continuing care, and terminal care) and factors associated with phase-specific incremental MM costs. The study was conducted from June 1, 2019, to April 30, 2021. Main Outcomes and Measures: Incremental MM costs were calculated for the disease lifetime and the following 4 phases of care: prediagnosis, initial, continuing care, and terminal. Results: Of the 4533 patients with MM included in the study, 2374 were women (52.4%), 3418 (75.4%) were White, and mean (SD) age was 75.8 (6.8) years (2313 [51.0%] aged ≥75 years). The characteristics of the control group were similar; however, mean (SD) age was 74.2 (8.8) years (2839 [62.6%] aged ≤74 years). Mean adjusted incremental MM lifetime costs were $184 495 (95% CI, $183 099-$185 968). Mean per member per month phase-specific incremental MM costs were estimated to be $1244 (95% CI, $1216-$1272) for the prediagnosis phase, $11 181 (95% CI, $11 052-$11 309) for the initial phase, $5634 (95% CI, $5577-$5694) for the continuing care phase, and $6280 (95% CI, $6248-$6314) for the terminal phase. Although inpatient and outpatient costs were estimated as the major cost drivers for the prediagnosis (inpatient, 55.8%; outpatient, 40.2%), initial care (inpatient, 38.1%; outpatient, 35.5%), and terminal (inpatient, 33.0%; outpatient, 34.6%) care phases, prescription drugs (44.9%) were the largest cost drivers in the continuing care phase. Conclusions and Relevance: The findings of this study suggest that there is substantial burden to Medicare associated with diagnosis and care among older adults with MM, and the cost of care and cost drivers vary across different phases of the cancer care continuum. The study findings might aid policy discussions regarding MM care and coverage and help further the development of alternative payment models for MM, accounting for differential costs across various phases of the disease continuum and their drivers.

Direct costs of antineoplastic and supportive treatment for progressive multiple myeloma in a tax-based health system.

Aim: To estimate current real-world costs of drugs and supportive care for the treatment of multiple myeloma in a tax-based health system. Methods: Forty-one patients were included from a personalized medicine study (2016-2019). Detailed information was collected from patient journals and hospital registries to estimate the total and mean costs using inverse probability weighting of censored data. Results: Total observed (censored) costs for the 41 patients was €8.84 million during 125 treatment years, with antineoplastic drugs as the main cost driver (€5.6 million). Individual costs showed large variations. Mean 3-year cost per patient from first progression was €182,103 (€131,800-232,405). Conclusion: Prediction of real-world costs is hindered by the availability of detailed costing data. Micro-costing analyses are needed for budgeting and real-world evaluation of cost-effectiveness.

Lay abstract In recent years, there has been a dramatic improvement in the treatment of multiple myeloma due to the introduction of new drugs. These drugs have significantly increased survival but have also had an immense impact on healthcare budgets. In this study, we used detailed treatment information for multiple myeloma patients in combination with billing data from the hospital pharmacy at a Danish hospital to calculate individual cost histories for both drugs and supportive care. Using these data, we estimated the mean 3-year cost of a multiple myeloma patient to be €182.103, but we also found large variation between patients, causing an uncertainty of €50.000 in either direction. We believe that detailed costing studies, similar to the present one, are necessary for evaluation of cost-effectiveness of drugs in clinical practice.

Survival, health care resource utilization and expenditures of first-line treatments for multiple myeloma patients ineligible for transplant in Taiwan.

BACKGROUND: We aimed to provide real-world information on survival, health care resource utilization (HCRU), and expenditures related to various first lines of therapy (1LOTs) in newly diagnosed multiple myeloma (NDMM) patients who were transplant ineligible (TI). PATIENTS AND METHODS: From the Taiwan National Health Insurance Database (2008-2016), we identified 1,511 NDMM-TI patients who had received 1LOT since June 2012. We categorized 1LOT regimens into four groups: bortezomib (V)+thalidomide (T), V, T, and non-V/T. Patients' characteristics were collected. The overall survival (OS), event-free survival (EFS), frequencies of HCRU (hospitalization, visiting outpatient and emergency departments), and related expenditures within one year after commencement of the 1LOT were evaluated and compared. RESULTS: The mean age of the included patients was 71.3 (SD 10.7) years, and 40.4% of patients had a CCI score ≥3. Most patients (747; 49.4%) were in the V+T group and, after adjusting for covariates, had a significantly longer OS (median, 22.2 months) and EFS (9.1 months) than those in the T group (12.6 and 4.5 months, respectively) and the non-V/T group (12.2 and 3.2 months, respectively), but they were mostly comparable with patients in the V group (23.8 and 6.6 months, respectively). Compared to those in the V+T group, patients in the T and non-V/T groups had 29% and 39% fewer outpatient visits and 15% and 24% lower total expenditure, respectively. CONCLUSION: Our real-world data consolidate evidence for the effectiveness of bortezomib-containing regimens as the 1LOT in NDMM-TI patients at the expense of more outpatient visits and higher total costs.

Economic burden of disease progression among multiple myeloma patients who have received transplant and at least one line of therapy in the US.

Effects of disease progression on healthcare resource utilization (HRU) and costs among multiple myeloma (MM) patients with ≥1 line of therapy (LOT) who received their first stem cell transplant (SCT) within 1 year of initial MM diagnosis were estimated using a large US claims database. Disease progression was defined as advancement to the next LOT, bone metastasis, hypercalcemia, soft tissue plasmacytoma, skeletal related events, acute kidney disease, or death within 12 months of LOT initiation. Annual HRU and costs in the first three LOTs (L1-L3) were compared for patients with versus without disease progression using inverse probability of treatment weighting to adjust for differences between groups in baseline characteristics. In all LOTs, mean annual hospitalizations and healthcare costs were greater for patients with versus without progression. Total incremental annual costs among patients with versus without progression in L1-L3 were $18,359, $87,055, and $71,917, respectively, among LOTs initiated between 2006 and 2018. In LOTs initiated between 2013 and 2018, the figures were $46,024, $100,329, and $101,942 in L1-L3, respectively. The economic burden of disease progression is substantial in this population of MM patients who underwent SCT and received systemic anti-myeloma therapy.

A descriptive cost-analysis of MYX.1/MCRN003, a phase 2 clinical trial evaluating high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone in relapsed and refractory multiple myeloma.

BACKGROUND: The prevalence of multiple myeloma is increasing and there is a need to evaluate escalating therapy costs (Canadian Cancer Statistics A, 2020). The MYX.1 phase II trial showed that high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone (wKCD) is efficacious in relapsed and refractory disease. We conducted a descriptive cost analysis, from the perspective of the Canadian public healthcare system, using trial data. METHODS: The primary outcome was the mean total cost per patient. Resource utilization data were collected from all 75 trial patients over a trial time horizon. Costs are presented in Canadian dollars (2020). RESULTS: The cost of treatment was calculated from the time of patient (pt) enrollment until the second data lock. The mean total cost was $203 336.08/pt (range $17 891.27-$505 583.55) Canadian dollars (CAD, where 1 CAD = 0.67 Euro (EUR)) and $14 081.45/pt per cycle. The median number of cycles was 15. The predominant cost driver was the cost of chemotherapy accounting for an average of $179 332.78/pt or $12 419.17/pt per cycle. Carfilzomib acquisition accounted for the majority of chemotherapy costs - $162 471.65/pt or $11 251.50/pt per cycle. Fifty-six percent (56%) of patients had at least one hospitalization during the trial period with an average cost of $12 657.86 per hospitalization. Three patients developed thrombotic microangiopathy (TMA) with an average cost of $18 863.32/pt including the cost of hospitalizations and therapeutic plasma exchange. CONCLUSIONS: High-dose wKCD is an active triplet regimen for relapsed and refractory multiple myeloma (RRMM) associated with reduced total cost compared with twice-weekly carfilzomib-based regimens.

Lessons Learned Treating Patients with Multiple Myeloma in Resource-Constrained Settings.

PURPOSE OF REVIEW: Based on personal experiences, recommendations for physicians treating patients with multiple myeloma (MM) in low- and middle-income countries (LMICs) are proposed. RECOMMENDATIONS: (1) Implement strategies to keep the patient in the best possible condition for the longest time, in addition to focusing on ways to avoid financial toxicity; (2) if lenalidomide is unavailable, start treatment with thalidomide and dexamethasone, include, if possible, bortezomib; (3) conduct an outpatient-based autologous stem cell transplantation (ASCT) in all eligible patients; (4) use thalidomide as post-ASCT maintenance treatment if lenalidomide is unavailable for the standard risk patients; (5) monitor monoclonal proteins with serum protein electrophoresis and free light chain measurements; (6) employ novel drugs in cases of relapsed or refractory disease; and (7) do not forget supportive therapy. The therapeutic recommendations to treat patients with MM are somewhat different for physicians working in LMICs, compared with those treating patients in high-income countries. These are relevant since more than 50% of the inhabitants of the world live in LMICs, thus indicating that the vast majority of patients with MM are being treated in resource-constrained settings. As time goes by, physicians may acquire the ability to analyze and express their feelings and experiences about topics in the practice of medicine in which they could have learned lessons (1). Since 1980, we have been treating patients with multiple myeloma (MM); to date, we have been personally involved in the study and treatment of more than 300 patients with this disease (2). Having gained experience dealing with MM patients in underprivileged circumstances, such as those prevailing in our country: México, having explored different ideas, treatments, and methods, and being aware of the financial implications which may impact our selection of therapeutic strategies and recommendations, we felt that it was appropriate to share in this article some of these ideas with practitioners around the world who are involved in the treatment of patients with MM in low- and middle-income countries (LMICs).

Cost-effectiveness of Novel Treatment Sequences for Transplant-Ineligible Patients With Multiple Myeloma.

Importance: Although the number of treatments for elderly patients with non-transplant-eligible (NTE) multiple myeloma (MM) has increased substantially, evidence is lacking on the clinical effectiveness and cost-effectiveness of novel treatment sequences. Objective: To determine the optimal sequence of treatment for patients with NTE MM from the perspective of the patient, physician, and society. Design, Setting, and Participants: Using data from a Dutch observational registry, this economic evaluation combined evidence from network meta-analyses in a patient-level simulation model and modeled time-to-event and types of events from a hospital perspective with a lifetime horizon. Data analysis was performed from June 2019 to September 2020. Interventions: Thirty treatment sequences, including up to 3 lines of therapy, were compared with bortezomib-melphalan-prednisone (VMP)-lenalidomide-dexamethasone (LenDex)-pomalidomide-dexamethasone (PomDex). Main Outcomes and Measures: The primary outcomes of the model were overall survival (OS), quality-adjusted life-years (QALYs), costs, and cost-effectiveness. Results: Sequences starting with daratumumab-VMP (second line: carfilzomib-lenalidomide-dexamethasone or elotuzumab-lenalidomide-dexamethasone) or bortezomib-melphalan-prednisone-thalidomide-maintenance bortezomib-thalidomide (VMPT-VT) (second line: daratumumab-lenalidomide-dexamethasone) had the largest expected OS (7.5 years), which is 3.5 additional life-years compared with VMP-LenDex-PomDex. Total costs per patient for these sequences ranged between $786 024 and $1 085 794. The sequence VMPT-VT-carfilzomib-lenalidomide-dexamethasone-panobinostat-bortezomib-dexamethasone had the most favorable cost-effectiveness ratio ($98 585 per life-year gained and $132 707 per QALY gained vs VMP-LenDex-PomDex). Conclusions and Relevance: These findings suggest that sequences including novel treatments were highly effective, but the cost-effectiveness ratios were above currently accepted willingness-to-pay thresholds. Treating MM with novel agents necessitates either a large increase in budget or a substantial reduction of drug costs by price negotiations, and these findings can support these reimbursement decisions and price negotiations.

The Impact of Socioeconomic Risk Factors on the Survival Outcomes of Patients With Newly Diagnosed Multiple Myeloma: A Cross-analysis of a Population-based Registry and a Tertiary Care Center.

BACKGROUND: Multiple myeloma (MM) is a heterogeneous clonal plasma cell disorder leading to differences in clinical outcomes such as overall survival (OS) among patients. We hypothesized that with expensive, novel therapeutic agents and paradigm shifts to maintain continuous therapy and improvement in OS, patients with MM are subject to the pressures of financial toxicity and the need for social support, which may be of prognostic importance. MATERIALS AND METHODS: In this study, we examined the records of 122,458 patients from the National Cancer Database (NCDB) to determine the significance of socioeconomic factors such as estimated annual household income and education level, which were based on the patient's ZIP Code and the United States Census Bureau's 5-year report from 2008 to 2012. These socioeconomic factors, in addition to marital status, were then assessed individually and as a cumulative socioeconomic score for prognostic significance in a cohort of 2543 patients treated at a tertiary care center utilizing known biologic risk factors, such as cytogenetic risk, International Staging System classification, and serum lactate dehydrogenase levels. RESULTS: Only marital status and estimated annual household income at diagnosis negatively impacted OS in a univariate analysis, but not in the context of a multivariable analysis incorporating known biologic risk factors. CONCLUSION: Future analyses in other academic and non-academic centers located in urban and rural regions are required to understand the socioeconomic drivers of OS disparity among patients with MM observed nationally.

The impact of changed treatment patterns in multiple myeloma on health-care utilisation and costs, myeloma complications, and survival: A population-based comparison between two time periods in Denmark.

OBJECTIVES: To evaluate health-care utilisation and costs, myeloma complications and survival in Danish patients with multiple myeloma (MM) before and after implementation of new early-line treatments in 2009. METHODS: Based on data from the Danish National Health Registers, 3518 patients diagnosed with MM during 2002-2005 or 2010-2013 and randomly matched control individuals were identified, and health-care utilisation and costs were estimated. RESULTS: Health-care utilisation showed a marked shift from inpatient admissions towards outpatient visits. From early to late period, the mean annual number of outpatient visits increased by 22% and 28% in patients <65 years and ≥65 years, respectively. Additionally, the mean annual outpatient service costs increased correspondingly from 17 001€ to 23 643€ in younger patients and from 11 317€ to 16 144€ in the elderly. Increasing outpatient costs were outbalanced by lower inpatient admission costs and the adjusted total mean annual costs decreased in younger patients, probably partly due to fewer myeloma complications. The five-year survival rates increased markedly in both younger (HR = 0.51) and elderly (HR = 0.69) patients. CONCLUSION: Despite the introduction of new expensive early-line MM treatments in 2009, health-care costs remained stable due to a shift in health-care utilisation towards outpatient clinic care and fewer complications.

A systematic review of economic evaluations of treatment regimens in multiple myeloma.

BACKGROUND: The expansion of advanced expensive therapeutic innovations for Multiple Myeloma (MM) led to increased disclosure of economic evaluations. The present analysis systematically reviewed and appraised the reporting quality of economic evaluations in MM. METHODOLOGY: A comprehensive literature search in Ovid, MEDLINE(R), PubMed, and Cochrane libraries was conducted for studies published in the past decade. Two independent authors performed study selection and data extraction in a standardized form. Study methodological quality assessment was performed using 10-item Drummond's tool. RESULTS: Of potentially eligible 1150 retrieved studies, 17 met eligibility criteria. Six evaluations (35%) were in newly diagnosed MM and 11 (65%) in relapse refractory (RR) MM. Nine studies (53%) embraced the payer's perspective, five (29%) adopted health care system, one (6%) societal and two did not report. Six (35%) employed partitioned survival model, 4(24%) discrete event simulation, 4(24%) Markov model and 2(12%) used decision tree model. The methodological quality has improved significantly; 16 (94%) studies comprehended a well-defined question by affirming the analysis perspective and examined both costs and outcomes while 13 (71%) provided a comprehensive description of competing alternatives. CONCLUSION: The addition of novel drugs to the treatment armamentarium of MM is considerably cost-effective. The evaluations became more frequent, methodological quality has improved in the last decade.

Persistent challenges with treating multiple myeloma early.

Over the past decade, 2 strategies have advanced the treatment of patients with multiple myeloma and its precursor diseases. First, the definition has changed to include patients without end organ damage, who previously would not have been treated. Second, there is widespread enthusiasm for treating high-risk, smoldering multiple myeloma. In this commentary, we explore the evidence supporting these therapeutic expansions. Although early treatment adds cost and therapeutic burden, it remains unknown whether survival and health-related quality of life are improved by early treatment. Herein, we consider the implications of diagnostic expansion in multiple myeloma.