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.

A U.S. Cost Analysis of Triplet Regimens for Patients with Previously Treated Multiple Myeloma.

BACKGROUND: In recent years, the FDA has approved several 3-agent (i.e., triplet) combinations for previously treated multiple myeloma (MM), and the National Comprehensive Cancer Network (NCCN) now recommends triplet regimens over doublets. Little is known about the real-world cost of triplet combinations because of the limited time that they have been on the market since FDA approval. Furthermore, traditional cost analyses developed to support market entrance rely on utilization assumptions that are difficult to validate when numerous comparators simultaneously enter the market. OBJECTIVE: To perform a 1-year cost analysis of novel triplets used for the treatment of patients with previously treated MM controlling for differences in utilization. METHODS: FDA-approved, NCCN-recommended (preferred and category 1 for previously treated MM) treatments included in the analysis were daratumumab plus lenalidomide plus dexamethasone (DARA/LEN/DEX), daratumumab plus bortezomib plus dexamethasone (DARA/BOR/DEX), elotuzumab plus lenalidomide plus dexamethasone (ELO/LEN/DEX), carfilzomib plus lenalidomide plus dexamethasone (CAR/LEN/DEX), and ixazomib plus lenalidomide plus dexamethasone (IXA/LEN/DEX). To control for market uptake, the model was designed to estimate the cost of treating an average patient over a 1-year time horizon. Drug administration and dosing, required comedications, postprogression therapy, monitoring requirements, and adverse event (AE) rates were based on FDA prescribing information or clinical trials. AEs ≥ grade 3 that occurred in ≥ 5% of patients were included. RED BOOK wholesale acquisition costs were used for drug acquisition costs. Costs of drug administration, AE management, and patient monitoring were based on the 2018 Center for Medicare & Medicaid Services payment rates or from published literature (inflated to 2018 U.S. dollars). The treatment duration for each regimen was estimated from modeled progression-free survival data; the 12-month progression-free survival rate was assumed to be equivalent to the probability that an average patient remained on therapy for at least 1 year after treatment initiation, which was used to estimate time-depended treatment-related costs. The probability of progression within 1 year of treatment initiation was used to inform the average postprogression therapy costs for each regimen. RESULTS: The estimated cost per patient for each triplet regimen was $13,890 (DARA/BOR/DEX), $22,231 (IXA/LEN/DEX), $24,322 (ELO/LEN/DEX), $26,410 (DARA/LEN/DEX), and $27,432 (CAR/LEN/DEX). Drug acquisition costs and treatment duration were the largest drivers of cost. Scenario analyses with plausible alternative input parameters found the maximum per month cost of therapy to be $30,657 (CAR/LEN/DEX) and the minimum per month cost of therapy to be $13,784 (DARA/BOR/DEX). CONCLUSIONS: This analysis controlled for differential utilization rates for 5 FDA-approved, NCCN-recommended triplet therapies for the treatment of previously treated MM. Of the examined regimens, treatment with DARA/BOR/DEX was estimated to have the lowest average monthly cost per patient, while CAR/LEN/DEX was the most expensive. As is common with modeling, some assumptions were necessary, and results may not be generalizable. DISCLOSURES: This study was funded by Janssen Scientific Affairs, which employs Maiese and funded Cornerstone Research Group, a health economic consulting group, to complete the cost analysis, interpret data, and develop the manuscript. Janssen was involved in the design of the analysis, interpretation of results, and manuscript development and approval. Grima is a founding partner of Cornerstone Research Group, which employs Hollmann, Goyert, and Moldaver. Hollmann, Goyert, and Moldaver were responsible for creation of the economic model. This work was peer-reviewed and presented as an abstract at the Lymphoma and Myeloma 2017 International Congress; October 26-28, 2017; New York, NY.

Evaluating Oncology Value-Based Frameworks in the U.S. Marketplace and Challenges in Real-World Application: A Multiple Myeloma Test Case.

BACKGROUND: With the continuous rise in costs for oncology drugs, the American Society of Clinical Oncology (ASCO), the Institute for Clinical and Economic Review (ICER), the Memorial Sloan Kettering Cancer Center's Drug Abacus (DrugAbacus), and the National Comprehensive Cancer Network (NCCN) have developed value-based frameworks (VBFs) to assist stakeholders in formulary and treatment decision-making processes. Since emerging VBFs have the potential to affect available treatment options for patients, it is important to understand the differences associated with these VBFs within various therapeutic areas. OBJECTIVES: To (a) compare VBFs across 3 therapeutic options for relapsed or refractory multiple myeloma (RRMM) and (b) identify challenges and limitations associated with real-world decision making using VBFs in the U.S. marketplace. METHODS: The values of regimens carfilzomib (CFZ), elotuzumab (ELO), and ixazomib (IX) were generated using the ASCO, NCCN, ICER, and DrugAbacus VBFs. These regimens, used for second- or third-line treatment of RRMM, shared a common comparator in clinical trials: lenalidomide + dexamethasone (LEN + DEX). ASCO's 2016 VBF, which incorporated clinical benefit, toxicity, and bonus points, was used to generate a net health benefit score, along with the drug wholesale acquisition cost, for each regimen compared with LEN + DEX. Results of the 2016 NCCN Evidence Blocks for multiple myeloma and the ICER 2016 report of treatment options for RRMM were extracted to generate the value of CFZ, ELO, and IX. No output was generated from DrugAbacus because of the lack of regimens included in the test case. Shortcomings associated with running the test case in RRMM for each VBF were also identified. RESULTS: Among the 3 therapeutic agents, CFZ, in combination with LEN + DEX, was the most valued. ASCO and ICER VBFs suggested that CFZ + LEN + DEX may be the most valued, followed by ELO + LEN + DEX and IX + LEN + DEX. NCCN suggested that LEN + DEX may be the most valued followed by CFZ + LEN + DEX, IX + LEN + DEX, and ELO + LEN + DEX. A number of shortcomings were noted across each VBF, such as complexities of drug evidence evaluation with the ASCO VBF, the inability to adjust the ICER and NCCN VBFs to specific populations, and subjectivity associated with the NCCN VBF and DrugAbacus. CONCLUSIONS: Although the test case provided some consensus on treatment decisions, there is much nuance and limitations with the VBFs available for RRMM. Clearer objectivity and better adaptability to specific treatment decisions are warranted. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose. All authors contributed to study concept and design, as well data collection and interpretation. Djatche and Goble wrote and revised the manuscript, along with Chun and Varga. Portions of this work have previously been presented at the AMCP Managed Care and Specialty Pharmacy Annual Meeting 2017 in Denver, Colorado, March 27-30, 2017, and at the ISPOR 22nd Annual International Meeting in Boston, Massachusetts, May 20-24, 2017.

Why Value Framework Assessments Arrive at Different Conclusions: A Multiple Myeloma Case Study.

As the United States transitions from a volume-based health care system to one that rewards value, new frameworks are emerging to help patients, providers, and payers assess the value of medical services and biopharmaceutical products. These value assessment frameworks are intended to support various types of health care decision making. They have the potential to substantially affect patients, whether as tools for shared decision making with their doctors, as an input to care pathways used by providers, or through payer use of the frameworks to make coverage or reimbursement decisions. Prominent among current U.S. value assessment frameworks are those developed by the American Society of Clinical Oncology, the Institute for Clinical and Economic Review, the Memorial Sloan Kettering Cancer Center, and the National Comprehensive Cancer Network. These frameworks generally reflect the interests and expertise of the organizations that developed them. The evidence, methodology, and intended use differ substantially across frameworks, which can lead to highly variable determinations of value for the same treatment therapy. To demonstrate this variability, we explored how these frameworks assess the value of treatment regimens for multiple myeloma. Cross-framework comparisons of multiple myeloma assessments were conducted, and consistency of findings was examined for 3 case studies. A discussion of the analysis explores why different frameworks arrive at different conclusions, whether those differences are cause for concern, and the resulting implications for framework readiness to support health care decision making. DISCLOSURES: Funding for this project was provided by the National Pharmaceutical Council. The authors are employees of the National Pharmaceutical Council, an industry-funded health policy research group that is not involved in lobbying or advocacy. Study concept and design were contributed by Westrich and Dubois, along with Buelt. Westrich took the lead in data collection, along with Dubois, and data interpretation was performed by all the authors. The manuscript was written by Westrich and Buelt, along with Dubois, and revised by all the authors.

Cost effectiveness of pomalidomide in patients with relapsed and refractory multiple myeloma in Sweden.

BACKGROUND: Multiple myeloma (MM) patients who have progressed following treatment with both bortezomib and lenalidomide have a poor prognosis. In this late stage, other effective alternatives are limited, and patients in Sweden are often left with best supportive care. Pomalidomide is a new anti-angiogenic and immunomodulatory drug for the treatment of MM. Our objective was to evaluate the cost effectiveness of pomalidomide as an add-on to best supportive care in patients with relapsed and refractory MM in Sweden. MATERIAL AND METHODS: We developed a health-economic discrete event simulation model of a patient's course through stable disease and progressive disease, until death. It estimates life expectancy, quality-adjusted life years (QALYs) and costs from a societal perspective. Effectiveness data and utilities were taken from the MM-003 trial comparing pomalidomide plus low-dose dexamethasone with high-dose dexamethasone (HIDEX). Cost data were taken from official Swedish price lists, government sources and literature. RESULTS: The model estimates that, if a patient is treated with HIDEX, life expectancy is 1.12 years and the total cost is SEK 179 976 (€19 100), mainly indirect costs. With pomalidomide plus low-dose dexamethasone, life expectancy is 2.33 years, with a total cost of SEK 767 064 (€81 500), mainly in drug and indirect costs. Compared to HIDEX, pomalidomide treatment gives a QALY gain of 0.7351 and an incremental cost of SEK 587 088 (€62 400) consisting of increased drug costs (59%), incremental indirect costs (33%) and other healthcare costs (8%). The incremental cost-effectiveness ratio is SEK 798 613 (€84 900) per QALY gained. CONCLUSION: In a model of late-stage MM patients with a poor prognosis in the Swedish setting, pomalidomide is associated with a relatively high incremental cost per QALY gained. This model was accepted by the national Swedish reimbursement authority TLV, and pomalidomide was granted reimbursement in Sweden.

Critical review of economic evaluations in multiple myeloma: an overview of the economic evidence and quality of the methodology.

Continued expansion in the availability of costly alternative therapies in multiple myeloma will enhance the role of economic evaluations in reimbursement decisions and amendments to the treatment guidelines. The quality of economic evaluations should be taken into account by clinicians involved in decision-making. A systematic review and critique of the methodology was performed to assess the trends and quality in economic evaluations in multiple myeloma to date. A literature search was conducted to identify full economic evaluations in multiple myeloma as of December 2009. Details of the economic evaluation methods applied were extracted. Each study underwent a quality assessment based on the Drummond checklist for appraisal of high-quality economic evaluations in health care. Eighteen published economic evaluations were identified. Stem cell transplantation in combination with intensive chemotherapy has been demonstrated to be cost-effective, while interferon alpha is generally ineffective at additional costs. Evaluations have become less frequent in the last decade, especially for newer therapies despite their important contribution to improvements in outcomes. The quality of the methodology applied and its documentation can be improved in many aspects. As users of the results of economic evaluations, clinicians involved in guiding decision-making should be critical of the quality of economic evaluations in multiple myeloma. To ensure access to and identification of high-quality studies, researchers conducting economic evaluations of future advances should strive towards evaluations that fulfil the Drummond criteria and are properly documented.

The costs of peripheral blood progenitor cell reinfusion mobilised by granulocyte colony-stimulating factor following high dose melphalan as compared with conventional therapy in multiple myeloma.

In a retrospective study, we calculated the treatment costs of 26 patients, who received either high dose melphalan combined with granulocyte colony-stimulating factor (G-CSF; filgrastim)(n = 7) or without G-CSF (n = 11) or alternatively, peripheral blood progenitor cell reinfusion (PBPC) mobilised by G-CSF following high dose melphalan. In comparison with the control group, a shortening of the pancytopenic period and platelet recovery was noticed in the PBPC group. This resulted in a reduction in hospital costs, diagnostics, laboratory services, total parenteral nutrition and transfusions. The average costs per treatment in the PBPC group amounted to about US$ 17,908 as compared to US$ 32,223 in the control group, implying a cost reduction of 44% when changing to PBPC reinfusion.