Health-related quality of life in patients with steroid-refractory acute graft-versus-host disease.

BACKGROUND: Evidence regarding health-related quality of life (HRQoL) in patients with steroid-refractory acute graft-versus-host disease (SR-aGvHD) is lacking. Evaluating HRQoL was a secondary objective of the HOVON 113 MSC trial. Here we describe the outcomes of the EQ-5D-5L, EORTC QLQ-C30, and FACT-BMT for all adult patients who completed these questionnaires at baseline (i.e., before the start of treatment; n = 26). METHODS: Descriptive statistics were used to describe baseline patient and disease characteristics, EQ-5D dimension scores and values, EQ VAS scores, EORTC QLQ-C30 scale/item and summary scores, and FACT-BMT subscale and total scores. RESULTS: The mean EQ-5D value was 0.36. In total, 96% of the patients reported problems with usual activities, 92% with pain/discomfort, 84% with mobility, 80% with self-care, and 72% with anxiety/depression. The mean EORTC QLQ-C30 summary score was 43.50. Mean scale/item scores ranged from 21.79 to 60.00 for functioning scales, from 39.74 to 75.21 for symptom scales, and from 5.33 to 91.67 for single items. The mean FACT-BMT total score was 75.31. Mean subscale scores ranged from 10.09 for physical well-being to 23.94 for social/family well-being. CONCLUSION: Our study showed that HRQoL in patients with SR-aGvHD is poor. Improving HRQoL and symptom management in these patients should be a top priority.

Assessment of Studies Evaluating Incremental Costs, Effectiveness, or Cost-Effectiveness of Systemic Therapies in Breast Cancer Based on Claims Data: A Systematic Review.

OBJECTIVES: Large secondary databases, such as those containing insurance claims data, are increasingly being used to compare the effects and costs of treatments in routine clinical practice. Despite their appeal, however, caution must be exercised when using these data. In this study, we aimed to identify and assess the methodological quality of studies that used claims data to compare the effectiveness, costs, or cost-effectiveness of systemic therapies for breast cancer. METHODS: We searched Embase, the Cochrane Library, Medline, Web of Science, and Google Scholar for English-language publications and assessed the methodological quality using the Good Research for Comparative Effectiveness principles. This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under number CRD42018103992. RESULTS: We identified 1251 articles, of which 106 met the inclusion criteria. Most studies were conducted in the United States (74%) and Taiwan (9%) and were based on claims data sets (35%) or claims data linked to cancer registries (58%). Furthermore, most included large samples (mean 17 130 patients) and elderly patients, and they covered various outcomes (eg, survival, adverse events, resource use, and costs). Key methodological shortcomings were the lack of information on relevant confounders, the risk of immortal time bias, and the lack of information on the validity of outcomes. Only a few studies performed sensitivity analyses. CONCLUSIONS: Many comparative studies of cost, effectiveness, and cost-effectiveness have been published in recent decades based on claims data, and the number of publications has increased over time. Despite the availability of guidelines to improve quality, methodological issues persist and are often inappropriately addressed or reported.

Cost of health care for paediatric patients with sickle cell disease: An analysis of resource use and costs in a European country.

BACKGROUND: While multiple studies have examined the cost of health care for one aspect of sickle cell disease care, few have focussed on the overall cost of comprehensive care for sickle cell disease. METHODS: We conducted a retrospective cohort study of children with sickle cell disease treated in a comprehensive care centre from 1 January 2015 to 31 December 2016. Health care utilisation of included patients was based upon data from two main sources. The clinical practice guideline was used to determine the expected resource use of routine comprehensive care (planned elective care), and the financial claims database was used to estimate real-world resource use associated with acute and inpatient care (additional care). RESULTS: A total of 125 children with sickle cell disease were analysed. Expenditures for these patients averaged €5049 [standard deviation (SD) €1634] per child per year. Total yearly costs per patient varied considerably, ranging from €669 to €84 010, and less than 15% of patients were responsible for 50% of the health care costs. The majority (37%) of costs was associated with inpatient hospital care, which increased by age group, 27% with diagnostics, 19% with treatment, 11% with outpatients' visits and 6% with emergency care. CONCLUSION: We have described real-world resource use and expenditures for children with sickle cell disease in a European comprehensive care centre. It seems that costs of a comprehensive approach with effective management in the outpatient setting is favourable when compared to episodic health care.

Efficacy of first-line treatments for multiple myeloma patients not eligible for stem cell transplantation: a network meta-analysis.

Decision making for patients with multiple myeloma (MM) not transplant eligible (NTE) is complicated by a lack of head-to-head comparisons of standards of care, the increase in the choice of treatment modalities, and the promising results that are rapidly evolving from studies with novel regimens. To support evidence-based decision making, we performed a network meta-analysis for NTE MM patients that synthesizes direct and indirect evidence and enables a comparison of all treatments. Relevant randomized clinical trials were identified by a systematic literature review in EMBASE®, MEDLINE®, MEDLINE®-in-Process and the Cochrane Central Register of Controlled Trials for January 1999 to March 2016. Efficacy outcomes [i.e. the hazard ratio (HR) and 95% confidence interval (95%CI) for progression-free survival] were extracted and synthesized in a random effects network-meta analysis. In total, 24 studies were identified including 21 treatments. According to the network-meta analysis, the HR for progression-free survival was favorable for all NTE MM treatments compared to dexamethasone (HR: 0.19-0.90). Daratumumab-bortezomib-melphalan-prednisone and bortezomib-melphalan-prednisone-thalidomide with bortezomib-thalidomide maintenance were identified as the most effective treatments (HR: 0.19, 95%CI: 0.08-0.45 and HR: 0.22, 95%CI: 0.10-0.51, respectively). HR and 95%CI for currently recommended treatments, bortezomib-lenalidomide-dexamethasone, bortezomib-melphalan-prednisone, and lenalidomide-dexamethasone compared to dexamethasone, were 0.31 (0.16-0.59), 0.39 (0.20-0.75), and 0.44 (0.29-0.65), respectively. In addition to identifying the most effective treatment options, we illustrate the additional value and evidence of network meta-analysis in clinical practice. In the current treatment landscape, the results of network meta-analysis may support evidence-based decisions and ultimately help to optimize treatment and outcomes of NTE MM patients.

Second-line treatment for acute graft-versus-host disease with mesenchymal stromal cells: A decision model.

OBJECTIVE: No standard second-line treatment exists for acute graft-versus-host disease steroid-refractory (SR-aGvHD), and long-term outcomes remain poor. Mesenchymal stromal cells (MSCs) have been evaluated as treatment, but no disease model (DM) exists that integrates and extrapolates currently available evidence. The aim of this study was to develop such a DM to describe the natural history of SR-aGvHD and to predict long-term outcomes. METHOD: The DM was developed in collaboration with experts in haematology-oncology. Subsequently, a model simulation was run. Input parameters for transition and survival estimates were informed by published data of clinical trials on MSC treatment for SR-aGvHD. Parametric distributions were used to estimate long-term survival rates after MSCs. RESULTS: The newly developed DM is a cohort model that consists of eight health states. For the model simulation, we obtained data on 327 patients from 14 published phase II trials. Due to limited evidence, DM structure was simplified and several assumptions had to be made. Median overall survival was 3.2 years for complete response and 0.5 years for no complete response. CONCLUSION: The DM provides a comprehensive overview on the second-line treatment pathway for aGvHD and enables long-term predictions that can be used to perform a cost-effectiveness analysis comparing any treatment for SR-aGvHD.

Balancing the Optimal and the Feasible: A Practical Guide for Setting Up Patient Registries for the Collection of Real-World Data for Health Care Decision Making Based on Dutch Experiences.

OBJECTIVES: The aim of this article was to provide practical guidance in setting up patient registries to facilitate real-world data collection for health care decision making. METHODS: This guidance was based on our experiences and involvement in setting up patient registries in oncology in the Netherlands. All aspects were structured according to 1) mission and goals ("the Why"), 2) stakeholders and funding ("the Who"), 3) type and content ("the What"), and 4) identification and recruitment of patients, data handling, and pharmacovigilance ("the How"). RESULTS: The mission of most patient registries is improving patient health by improving the quality of patient care; monitoring and evaluating patient care is often the primary goal ("the Why"). It is important to align the objectives of the registry and agree on a clear and functional governance structure with all stakeholders ("the Who"). There is often a trade off between reliability, validity, and specificity of data elements and feasibility of data collection ("the What"). Patient privacy should be carefully protected, and address (inter-)national and local regulations. Patient registries can reveal unique safety information, but it can be challenging to comply with pharmacovigilance guidelines ("the How"). CONCLUSIONS: It is crucial to set up an efficient patient registry that serves its aims by collecting the right data of the right patient in the right way. It can be expected that patient registries will become the new standard alongside randomized controlled trials due to their unique value.

A cost-effectiveness analysis of real-world treatment for elderly patients with multiple myeloma using a full disease model.

OBJECTIVES: To study the impact of novel treatments for elderly (≥66 yr) patients with multiple myeloma (MM) in daily practice by comparing real-world effects [overall survival (OS) and quality-adjusted life years (QALYs)] and costs over time. Also, we calculate cost-effectiveness of treatment sequences commonly prescribed to predict effects and costs if patients had received a different treatment sequence. METHODS: Real-world data including patient and disease characteristics, treatment information and resource use were collected from 1054 elderly patients with MM. Patients received first-line treatment during 2004-2007 (cohort 1) and 2008-2013 (cohort 2). The two cohorts were compared using a patient-level simulation (PLS) model comprising regression models which used patient and disease characteristics to estimate time to next treatment and death. Effects and costs from cohort 2 were compared to 4 commonly prescribed real-world sequences. RESULTS: Utilisation of novel agents was higher for cohort 2 compared to cohort 1. Modelled average OS for cohort 1 was 38 months (median 25) and total costs €44,200. OS for cohort 2 was 42 months (median 28) and total costs €69,017. The model identified potential OS gains if all patients were to be treated using combinations containing thalidomide, lenalidomide and bortezomib in that particular order. This sequence had, compared to real-world treatment, the most favourable incremental cost-effectiveness ratio, €24,618 per life year gained and €34,875 per QALY. CONCLUSIONS: Our patient-level model enabled to study the effects and costs of entire treatment sequences and to compare real-world treatment patterns over time. Increased utilisation of novel agents improved survival and increased costs for real-world patients with MM in the Netherlands.

Cost-effectiveness of rituximab as maintenance treatment for relapsed follicular lymphoma: results of a population-based study.

OBJECTIVES: On the basis of two population-based registries, our study aims to calculate the real-world cost-effectiveness of rituximab maintenance compared with observation in relapsed or refractory follicular lymphoma patients who responded to second-line chemotherapy. METHODS: Data were obtained from the EORTC20981 trial, the Netherlands Cancer Registry and two population-based registries. A Markov model was developed to calculate cost per life year gained (LYG) and quality-adjusted life years (QALYs) for three scenarios. RESULTS: Our real-world patients were (62 years) 6 to 7 years older and had higher complete response rates to second-line chemotherapy than the trial population. Differences between the real-world rituximab and observation group were observed for second-line chemotherapy and disease progression. Groups were more balanced after using propensity matching. Relying entirely on updated trial results (scenario1) in combination with local cost data resulted in ratios of €11,259 per LYG and €12,655 per QALY. For scenario2, consisting of trial efficacy and matched real-world costs, ratios of €21,202 per LYG and €23,821 per QALY were calculated. Using real-world matched evidence (scenario3) for both effectiveness and costs showed ratios of €10,591 per LYG and €11,245 per QALY. CONCLUSION: Although differences in real-world and trial population were found, using real-world data as well as results from long-term trial follow-up showed favourable ICERs for rituximab maintenance. Nevertheless, results showed that caution is required with data synthesis, interpretation and generalisability of results. As different scenarios provide answers to different questions, we recommend healthcare decision-makers to recognise the importance of calculating several cost-effectiveness scenarios.

Policymaker, please consider your needs carefully: does outcomes research in relapsed or refractory multiple myeloma reduce policymaker uncertainty regarding value for money of bortezomib?

INTRODUCTION: Dutch policy regulations require outcomes research for the assessment of appropriate drug use and cost-effectiveness after 4 years of temporary reimbursement. We investigated whether outcomes research reduced policymaker uncertainty regarding the question whether the costs are worth public funding. METHODS: Our cohort study included 139 patients with relapsed/refractory multiple myeloma who were treated outside of a clinical study; 72 received bortezomib and 67 did not receive bortezomib. Detailed data were retrospectively collected from medical records in 38% of Dutch hospitals. RESULTS: All patients received second-line treatment; 65%, 40%, and 14%, received three, four, or five or more lines of therapy. Neither a specific treatment sequence nor an appropriate comparator could be identified because of large variation in regimes. Kaplan-Meier curves showed an increased overall survival (mean [median] 29.5 [33.2] vs. 28.0 [21.6] months) for patients treated with bortezomib (Wilcoxon P = 0.01). Total mean costs were €81,626 (range €17,793-€229,783) and €52,760 (range €748-€179,571) for patients receiving bortezomib and patients not receiving bortezomib, respectively. Patients treated with bortezomib, however, were not comparable to other patients despite attempts to correct for confounding. Therefore, it was impossible to develop a feasible model to obtain a valid incremental cost-effectiveness estimate. CONCLUSIONS: It was possible to develop evidence on bortezomib's use, effects, and costs in everyday practice. Much uncertainty, however, remained regarding its cost-effectiveness. Policymakers should carefully consider whether outcomes research sufficiently decreases uncertainty or whether other options (e.g., finance- and/or outcomes-based risk-sharing arrangements) are more appropriate to ensure sufficient value for money of expensive drugs.

Changes in income and employment after diagnosis among patients with multiple myeloma in The Netherlands.

OBJECTIVE: Due to new treatment options, survival rates in multiple myeloma (MM) are improving. Consequently, maintaining work and income is becoming more important for patients and society. Therefore, we aimed to explore the change in income and employment in patients with MM. METHODS: Data from the Netherlands Cancer Registry of MM patients diagnosed between 2012 and 2017 were merged with socioeconomic data from Statistics Netherlands. Descriptive statistics were used to analyse total income, income from employment, and accumulated income before and after diagnosis. RESULTS: Income from employment decreased by 45% in MM patients, between 1 year before and 4 years after diagnosis Four years after diagnosis, 35% of the patients were still employed, with an accumulated 5-year productivity loss of €121 million. Higher income loss from employment and job loss was observed in female patients, patients with more extensive disease, or those not treated with autologous stem cell transplant. CONCLUSION: Loss of (income from) employment among patients with MM was high, causing financial burden on the patient and society. With improving survival in MM, more research and awareness are needed to better assess the importance of income and work for MM patients and society.

Costs of Newly Funded Proton Therapy Using Time-Driven Activity-Based Costing in The Netherlands.

BACKGROUND: Proton therapy (PT) has characteristics that enable the sparing of healthy, non-cancerous tissue surrounding the radiotherapy target volume better from radiation doses than conventional radiotherapy for patients with cancer. While this innovation entails investment costs, the information about the treatment costs per patient, especially during the start-up phase, is limited. This study aims to calculate the costs of PT at a single center during the start-up phase in the Netherlands. METHODS: The cost of PT per patient was estimated for the treatment indications, head and neck cancer, breast cancer, brain cancer, thorax cancer, chordoma and eye melanoma. A time-driven activity-based costing analysis (TDABC), a methodology that calculates the costs of consumed healthcare resources by a patient, was conducted in a newly established PT center in the Netherlands (HPTC). Both direct (e.g., the human resource costs for medical staff) and indirect costs (e.g., the operating/interest costs, indirect human resource costs and depreciation costs) were included. A scenario analysis was conducted for short-term (2021), middle-term (till 2024) and long-term (after 2024) predicted patient numbers in the PT center. RESULTS: The total cost of PT in 2020 at the center varied between EUR 12,062 for an eye melanoma course and EUR 89,716 for a head and neck course. Overall, indirect costs were the largest cost component. The high indirect costs implied the potential of the scale of economics; according to our estimation, the treatment cost could be reduced to 35% of the current cost when maximum treatment capacity is achieved. CONCLUSION: This study estimated the PT cost delivered in a newly operated treatment center. Scenario analysis for increased patient numbers revealed the potential for cost reductions. Nevertheless, to have an estimation that reflects the matured cost of PT which could be used in cost-effectiveness analysis, a follow-up study assessing the full-fledged situation is recommended.

Cost-Effectiveness of Abemaciclib in Early Breast Cancer Patients: One Size Fits All or Tailoring to Patients' Needs?

Purpose: The addition of two years of abemaciclib treatment to standard adjuvant endocrine therapy in all patients with high risk ER+, HER2- early breast cancer (EBC) has been approved by the US Food and Drug Administration (FDA). Pre-selection of patients with an immediate risk of recurrence within the group of clinically high risk patients using detection of minimal residual disease (MRD) using patient-informed circulating tumor DNA assays during follow-up could enhance efficacy. Here, we investigate the cost-effectiveness of the addition of two years abemaciclib in all high risk HR+, HER2- patients and in MRD-guided high risk patients only. Methods: Two semi-Markov models were developed to evaluate the cost-effectiveness of adding two years of abemaciclib compared to "standard treatment": 1) "abemaciclib all" and 2) "MRD-guided abemaciclib" using MRD-guidance. Data of the MonarchE trial were used to model the invasive disease-free survival (iDFS). Since iDFS and overall survival (OS) data of abemaciclib were currently limited, abemaciclib effects were extrapolated using a favorable, intermediate and unfavorable effect scenario. Results: The addition of abemaciclib in all high-risk EBC patients prolonged iDFS slightly (0.04 additional quality adjusted life years (QALYs)) and led to higher costs compared to standard ET, leading to a high incremental cost effectiveness ratio (ICER) of €1,551,876/QALY. Neither the favorable effect scenario (additional 1.09 QALYs) was cost-effective (ICER €62,935/QALY), using a willingness-to-pay threshold of €50,000/QALY. The "MRD-guided abemaciclib" strategy resulted in lower costs and an increase in QALYs (1.27) compared to "standard treatment" in the unfavorable effect scenario. Conclusion: The addition of abemaciclib to adjuvant endocrine therapy in all high-risk ER+, HER2- EBC patients is not cost-effective. However, using MRD detection to justify the addition of abemaciclib treatment dominates standard treatment in this cost-effectiveness analysis. Further evaluation of MRD detection in EBC by means of prospective clinical trials assessing clinical utility is recommended and promising in terms of cost-effectiveness.

Cost-Effectiveness Analysis of MammaPrint® to Guide the Use of Endocrine Therapy in Patients with Early-Stage Breast Cancer.

BACKGROUND: Gene expression profiling tests can predict the risk of disease recurrence and select patients who are expected to benefit from therapy, while allowing other patients to forgo therapy. For breast cancers, these tests were initially designed to tailor chemotherapy decisions, but recent evidence suggests that they may also guide the use of endocrine therapy. This study evaluated the cost effectiveness of a prognostic test, MammaPrint®, to guide the use of adjuvant endocrine therapy in patients eligible according to Dutch treatment guidelines. METHODS: We constructed a Markov decision model to calculate the lifetime costs (in 2020 Euros) and effects (survival and quality-adjusted life-years) of MammaPrint® testing versus usual care (endocrine therapy for all patients) in a simulated cohort of patients. The population of interest includes patients for whom MammaPrint® testing is currently not indicated, but for whom it may be possible to safely omit endocrine therapy. We applied both a health care perspective and a societal perspective and discounted costs (4%) and effects (1.5%). Model inputs were obtained from published research (including randomized controlled trials), nationwide cancer registry data, cohort data and publicly available data sources. Scenario and sensitivity analyses were conducted to explore the impact of uncertainty around input parameters. Additionally, threshold analyses were performed to identify under which circumstances MammaPrint® testing would be cost effective. RESULTS: Adjuvant endocrine therapy guided by MammaPrint® resulted in fewer side effects, more (quality-adjusted) life-years (0.10 and 0.07 incremental QALYS and LYs, respectively) and higher costs (€18,323 incremental costs) compared with the usual care strategy in which all patients receive endocrine therapy. While costs for hospital visits, medication costs and productivity costs were somewhat higher in the usual care strategy, these did not outweigh costs of testing in the MammaPrint® strategy. The incremental cost-effectiveness ratio was €185,644 per QALY gained from a healthcare perspective and €180,617 from a societal perspective. Sensitivity and scenario analyses showed that the conclusions remained the same under changed input parameters and assumptions. Our results show that MammaPrint® can become a cost-effective strategy when either the price of the test is reduced (> 50%), or the proportion of patients for which treatment is altered (i.e. those with ultra-low risk) increases to > 26%. CONCLUSION: Standard MammaPrint® testing to guide the use of endocrine therapy in our simulated patient population appears not to be a cost-effective strategy compared with usual care. The cost effectiveness of the test can be improved by reducing the price or preselecting a population more likely to benefit from the test.

Changes in survival in de novo metastatic cancer in an era of new medicines.

BACKGROUND: Over the past decades, the therapeutic landscape has markedly changed for patients with metastatic solid cancer, yet few studies have evaluated its effect on population-based survival. The objective of this study was to evaluate the change in survival of patients with de novo metastatic solid cancers during the last 30 years. METHODS: For this retrospective study, data from almost 2 million patients diagnosed with a solid cancer between January 1, 1989, and December 31, 2018, were obtained from the Netherlands Cancer Registry, with follow-up until January 31, 2021. We classified patients as with or without de novo metastatic disease (M1 or M0, respectively) at diagnosis and determined the proportion with M1 disease over time. Changes in age-standardized net survival were calculated as the difference in the 1- and 5-year survival rates of patients diagnosed in 1989-1993 and 2014-2018. RESULTS: Different cancers showed divergent trends in the proportion of M1 disease and increases in net survival for M1 disease (approximately 0-50 percentage points at both 1 and 5 years). Patients with gastrointestinal stromal tumors saw the largest increases in 5-year survival, but we also observed substantial 5-year survival increases for patients with neuroendocrine tumors, melanoma, prostate cancer, and breast cancer. CONCLUSION: Over 30 years, the survival of patients with de novo M1 disease modestly and unevenly increased among cancers. Metastatic cancer still remains a very lethal disease. Next to better treatment options, we call for better preventive measures and early detection to reduce the incidence of metastatic disease.

Medical Resource Use and Medical Costs for Radiotherapy-Related Adverse Effects: A Systematic Review.

BACKGROUND: Despite the need for a proper economic evaluation of new radiotherapies, the economic burden of radiotherapy-induced adverse effects remains unclear. A systematic review has been conducted to identify the existing evidence of healthcare resource use and costs related to radiotherapy-induced adverse effects and also to provide recommendations for including this evidence in economic evaluations. METHODS: This systematic review of healthcare resource use and/or medical costs related to radiotherapy-induced adverse effects was performed up until 2020, focusing on patients with head and neck cancer, brain cancer, prostate cancer, eye cancer and breast cancer. RESULTS: Resource use for treating the same adverse effects varied considerably across studies; for instance, the cost for mucositis ranged from USD 2949 to USD 17,244. This broad range could be related to differences in (1) severity of adverse effects in the study population, (2) study design, (3) cost estimation approach and (4) country and clinical practice. CONCLUSIONS: Our findings revealed unignorable differences for the same adverse effects, which implied that the potential for the economic burden of adverse effects was being overestimated or underestimated in economic evaluation for radiotherapy.

A Systematic Review of Cost-Effectiveness Analyses of Novel Agents in the Treatment of Multiple Myeloma.

BACKGROUND: Novel therapies for multiple myeloma (MM) promise to improve outcomes but are also associated with substantial increasing costs. Evidence regarding cost-effectiveness of novel treatments is necessary, but a comprehensive up-to-date overview of the cost-effectiveness evidence of novel treatments is currently lacking. METHODS: We searched Embase, Medline via Ovid, Web of Science and EconLIT ProQuest to identify all cost-effectiveness evaluations of novel pharmacological treatment of MM reporting cost per quality-adjusted life year (QALY) and cost per life year (LY) gained since 2005. Quality and completeness of reporting was assessed using the Consolidated Health Economic Evaluation Reporting Standards. RESULTS: We identified 13 economic evaluations, comprising 32 comparisons. Our results show that novel agents generate additional LYs (range: 0.311-3.85) and QALYs (range: 0.1-2.85) compared to backbone regimens and 0.02 to 1.10 LYs and 0.01 to 0.91 QALYs for comparisons between regimens containing two novel agents. Lifetime healthcare costs ranged from USD 60,413 to 1,434,937 per patient. The cost-effectiveness ratios per QALY gained ranged from dominating to USD 1,369,062 for novel agents compared with backbone therapies and from dominating to USD 618,018 for comparisons between novel agents. CONCLUSIONS: Cost-effectiveness ratios of novel agents were generally above current willingness-to-pay thresholds. To ensure access, cost-effectiveness should be improved or cost-effectiveness ratios above current thresholds should be accepted.

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.

Cost-effectiveness of lenalidomide plus rituximab versus rituximab monotherapy in patients with previously treated follicular lymphoma: a societal view.

INTRODUCTION: Efficacy of lenalidomide plus rituximab (R-LEN) compared to rituximab monotherapy (R-mono) for patients with previously treated follicular lymphoma (FL) was investigated in AUGMENT (NCT01938001). Our aim was to evaluate the cost-effectiveness of R-LEN versus R-mono in this setting from a Dutch perspective. AREAS COVERED: Cost-effectiveness was assessed through a partitioned survival model from three perspectives (i.e. societal, healthcare, and societal, including future non-medical costs). Patient-level data from AUGMENT informed effectiveness parameters (i.e. long-term survival) and health state utilities. Resource use and prices were based on AUGMENT and the literature. Clinical experts validated efficacy input parameters and results. Uncertainty was explored through sensitivity and scenario analyses. EXPERT OPINION: R-LEN resulted in 1.7 incremental discounted quality-adjusted life years (QALYs). Total incremental discounted costs were 67,161 EUR from a societal perspective. In conclusion, R-LEN was cost-effective at a willingness-to-pay (WTP) threshold of 50,000 EUR/QALY in the base-case analyses(incremental cost-effectiveness ratio = 40,493 EUR/QALY). Scenario and sensitivity analyses indicated some level of uncertainty regarding this conclusion, depending on the chosen WTP-threshold and perspective.