[Pharmacoeconomic analysis of anti-angiogenic drugs for diabetic macular edema]. / Farmakoekonomicheskii analiz primeneniya antiangiogennykh preparatov pri diabeticheskom makulyarnom oteke.

Diabetic macular edema (DME) is a degenerative disease of the macular area in diabetes mellitus and can lead to vision loss, disability, and significantly reduced quality of life. Faricimab is the only bispecific antibody for DME therapy that targets two pathogenic pathways (Ang-2 and VEGF-A). PURPOSE: This study comparatively evaluates the clinical and economic feasibility of faricimab and other angiogenesis inhibitors in patients with DME. MATERIAL AND METHODS: This article analyzed literature on the efficacy and safety of intravitreal injections (IVI) of ranibizumab 0.5 mg, aflibercept 2 mg, and faricimab 6 mg. A model of medical care was developed for patients with DME receiving anti-angiogenic therapy. Pharmacoeconomic analysis was performed using cost minimization and budget impact analysis (BIA) methods. Modeling time horizon was 2 years. The research was performed from the perspective of the healthcare system of the Russian Federation. RESULTS: The efficacy and safety of faricimab in a personalized regimen (up to one IVI in 16 weeks) are comparable to those of aflibercept and ranibizumab, administered in various regimens. The use of faricimab is associated with the lowest number of IVIs. Over 2 years, the maximum costs of drug therapy were associated with the use of ranibizumab (about 914 thousand rubles), while the minimum costs were associated with the use of faricimab (614 thousand rubles). The reduction in inpatient care costs with faricimab therapy was 36% compared to aflibercept (216 and 201 thousand rubles in inpatient and day hospitals, respectively) and 82% compared to ranibizumab (486 and 451 thousand rubles in inpatient and day hospitals, respectively). BIA demonstrated that the use of faricimab will reduce the economic burden on the healthcare system by 11.3 billion rubles (9.8%) over 2 years. CONCLUSION: The use of faricimab is a cost-effective approach to treatment of adult patients with DME in Russia.

Cost-effectiveness Analysis of Tisagenlecleucel Versus Blinatumomab in Children and Young Adults with Acute Lymphoblastic Leukemia: Partitioned Survival Model to Assess the Impact of an Outcome-Based Payment Arrangement.

OBJECTIVE: This research assesses the impact of an outcome-based payment arrangement (OBA) linking complete remission (CR) to survival as a means of maintaining cost-effectiveness for a chimeric antigen receptor T cell (CAR-T) therapy in young patients with acute lymphoblastic leukemia (ALL). METHODS: A partitioned survival model (PSM) was used to model the cost-effectiveness of tisagenlecleucel versus blinatumomab in ALL from the Australian healthcare system perspective. A decision tree modeled different OBAs by funneling patients into a series of PSMs based on response. Outcomes were informed by individual patient data, while costs followed Australian treatment practices. Costs and quality-adjusted life years (QALYs) were combined to calculate a single incremental cost-effectiveness ratio (ICER), reported in US dollars (2022) at a discount rate of 5% on costs and outcomes. RESULTS: For the base case, incremental costs and benefit were $379,595 and 4.27 QALYs, giving an ICER of $88,979. The ICER was most sensitive to discount rate ($57,660-$75,081), "cure point" ($62,718-$116,206) and extrapolation method ($76,018-$94,049). OBAs had a modest effect on the ICER when response rates varied. A responder-only payment was the most effective arrangement for maintaining the ICER ($88,249-$89,434), although this option was associated with the greatest financial uncertainty. A split payment arrangement (payment on infusion followed by payment on response) reduced variability in the ICER ($82,650-$99,154) compared with a single, upfront payment ($77,599-$107,273). CONCLUSION: OBAs had a modest impact on reducing cost-effectiveness uncertainty. The value of OBAs should be weighed against the additional resources needed to administer such arrangements, and importantly overall cost to government.

Cost-minimization analysis of recombinant factor VIII Fc versus emicizumab for treating patients with hemophilia A without inhibitors in Europe.

BACKGROUND AND OBJECTIVE: A cost-minimization model was developed to compare recombinant factor VIII Fc (rFVIIIFc) and emicizumab as prophylaxis for hemophilia A without inhibitors. METHODS: The model was based on 100 patients from the healthcare payer perspective in the UK, France, Italy, Spain, and Germany (5-year time horizon). Costs included: drug acquisition; emicizumab wastage by bodyweight (manufacturer's dosing recommendations); and additional FVIII for breakthrough bleeds. Scenario analyses (UK only): reduced emicizumab dosing frequency; and emicizumab maximum wastage. RESULTS: Total incremental 5-year savings for rFVIIIFc rather than emicizumab use range from €89,320,131 to €149,990,408 in adolescents/adults (≥12 years) and €173,417,486 to €253,240,465 in children (<12 years). Emicizumab wastage accounts for 6% of its total cost in adolescents/adults and 26% in children. Reducing the emicizumab dosing frequency reduces the incremental cost savings with rFVIIIFc, but these remain substantial (adolescents/adults, >€92 million; children >€32 million). Maximum emicizumab wastage increases by 86% and 106%, respectively, increasing the incremental cost savings with rFVIIIFc to €125,352,125 and €105,872,727, respectively. CONCLUSION: Based on cost-minimization modeling, rFVIIIFc use for hemophilia A prophylaxis in patients without inhibitors is associated with substantial cost savings in Europe, reflecting not only higher acquisition costs of emicizumab, but also other costs including wastage related to available vial sizes.

A comparison between on-demand usage of rFVIIa vs prophylaxis use of emicizumab in high titer inhibitory hemophilia A patients in Iran: A cost-utility analysis.

BACKGROUND: Hemophilia A (HA) is an inherited X-linked bleeding disease with costly treatment, especially for high titer inhibitory patients. Emicizumab, a new humanized bispecific antibody, has been approved for use to prevent or reduce the frequency of bleeding episodes in HA patients with inhibitors. This study evaluated the cost-utility of emicizumab prophylaxis (EP) in comparison with recombinant factor VII activated on-demand treatment in HA patients with inhibitors. METHODS: A life-time Markov model with payer and societal perspectives was developed in different age groups with different annual bleeding rates (ABR). Efficacy of treatments were extracted from HAVEN trials. Utilities were retrieved from published evidence. Costs were calculated based on Iran food and drug administration official website, national tariff book for medical services and hospital data. One-way deterministic sensitivity analysis was performed. RESULTS: EP was dominant choice in comparison with on-demand administration of recombinant factor VII activated in all age groups with ABR 20 and 25, and it remained dominant in patients with age 2 and age 12 at start point with ABR 16 and 17. The reported incremental cost-effectiveness ratio for the group with ABR 18 at the age 20, was 12,936 United States Dollars which is lower than the acceptable threshold of cost-effectiveness in Iran (1-3 gross domestic product per capita) and EP can be considered as cost-effective choice in this scenario. CONCLUSION: EP was found to be a dominant and cost-effective choice for Iranian HA patients with factor VIII inhibitors with ABR 18 and above with considerable cost saving.

Does Cost-Effectiveness Analysis Overvalue Potential Cures? Exploring Alternative Methods for Applying a "Shared Savings" Approach to Cost Offsets.

OBJECTIVES: To evaluate alternative methods to calculate and/or attribute economic surplus in the cost-effectiveness analysis of single or short-term therapies. METHODS: We performed a systematic literature review of articles describing alternative methods for cost-effectiveness analysis of potentially curative therapies whose assessment using traditional methods may suggest unaffordable valuations owing to the magnitude of estimated long-term quality-adjusted life-year (QALY) gains or cost offsets. Through internal deliberation and discussion with staff at the Health Technology Assessment bodies in England and Canada, we developed the following 3 alternative methods for further evaluation: (1) capping annual costs in the comparator arm at $150 000 per year; (2) "sharing" the economic surplus with the health sector by apportioning only 50% of cost offsets or 50% of cost offsets and QALY gains to the value of the therapy; and (3) crediting the therapy with only 12 years of the average annual cost offsets or cost offsets and QALY gains over the lifetime horizon. The impact of each alternative method was evaluated by applying it in an economic model of 3 hypothetical condition-treatment scenarios meant to reflect a diversity of chronicity and background healthcare costs. RESULTS: The alternative with greatest impact on threshold price for the fatal pediatric condition spinal muscular atrophy type 1 was the 12-year cutoff scenario. For a hypothetical one-time treatment for hemophilia A, capping cost offsets at $150 000 per year had the greatest impact. For chimeric antigen receptor T-cell treatment of non-Hodgkin's lymphoma, capping cost offsets or using 12-year threshold had little impact, whereas 50% sharing of surplus including QALY gains and cost offsets greatly reduced threshold pricing. CONCLUSIONS: Health Technology Assessment bodies and policy makers will wrestle with how to evaluate single or short-term potentially curative therapies and establish pricing and payment mechanisms to ensure sustainability. Scenario analyses using alternative methods for calculating and apportioning economic surplus can provide starkly different assessment results. These methods may stimulate important societal dialogue on fair pricing for these novel treatments.

The effectiveness and value of emicizumab and valoctocogene roxaparvovec for the management of hemophilia A without inhibitors.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Agboola, Rind, Herron-Smith, and Pearson are employed by ICER. Walton and Quach, through the University of Illinois at Chicago, received funding from ICER for development of the economic model described in this report.

Bispecific antibodies in acute lymphoblastic leukemia therapy.

INTRODUCTION: Blinatumomab, first in a class of bispecific T-cell engagers, revolutionized treatment paradigm of B-cell precursor relapsed/refractory or minimal residual disease positive acute lymphoblastic leukemia (ALL) in adults and children, inducing deep remissions in a proportion of patients. However, significant numbers of patients do not respond or eventually relapse. Strategies for improvement of treatment outcomes are required. AREAS COVERED: This review discusses the main structural and functional features of blinatumomab, and its place in the treatment of ALL. Furthermore, prospects to increase the efficacy of blinatumomab are addressed. The developments in the field of bispecific antibodies and their possible implications for treatment of ALL are reviewed. EXPERT OPINION: Better understanding the mechanisms of response and resistance to blinatumomab might help us to identify the group of patients benefiting most from treatment and to spare potentially toxic subsequent treatment strategies. Data emerging from ongoing clinical trials might change the treatment landscape of ALL and beyond. Early use of blinatumomab in frontline protocols with more advantageous treatment sequences and in combination with other targeted therapies might reduce the failure rates. Exponentially increasing number of novel treatment options and their possible combinations might complicate treatment decision-making without data from randomized trials.

The societal burden of haemophilia A. III - The potential impact of emicizumab on costs of haemophilia A in Australia.

INTRODUCTION: Emicizumab is a humanized monoclonal modified IgG4 antibody with bispecific antibody structure bridging Factor IXa and Factor X. Emicizumab has demonstrated efficacy and safety in adults, adolescents and paediatrics with HA, with or without inhibitors to Factor VIII (FVIII). There is currently no evidence that reports on the potential impact of the introduction of emicizumab on the societal costs of haemophilia A (HA). The purpose of this study was to explore the cost impact associated with the introduction of emicizumab on the current societal costs of people with HA (PwHA) in Australia. METHODS: We conducted an analysis of the impact of emicizumab on societal costs, based on changes in the direct and indirect costs incurred by PwHA. Potential impacts of emicizumab on outcomes in PwHA were modelled based on HAVEN 1, HAVEN 2 and HAVEN 3 studies. We assumed that eligible PwHA commenced use of emicizumab on 1 January 2018. The impact of emicizumab on costs of HA in Australia males was then estimated for the 12-month period to 31 December 2018. RESULTS: Overall, uptake of emicizumab in its first year of use reduces annual costs associated with moderate/severe HA by AUD$69.197M (62.3%). This reflects 64.2% reduction in the cost of FVIII blood products and 92% reduction in cost of bypassing agents. CONCLUSION: The cost of emicizumab is likely to offset some or all of the projected reductions in treatment costs. However, we also found 30.7% reduction in non-treatment direct costs (AUD$3.771M) and 19.1% reduction in indirect costs (AUD$2.732M).

Concepts in immuno-oncology: tackling B cell malignancies with CD19-directed bispecific T cell engager therapies.

The B cell surface antigen CD19 is a target for treating B cell malignancies, such as B cell precursor acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma. The BiTE® immuno-oncology platform includes blinatumomab, which is approved for relapsed/refractory B cell precursor acute lymphoblastic leukemia and B cell precursor acute lymphoblastic leukemia with minimal residual disease. Blinatumomab is also being evaluated in combination with other agents (tyrosine kinase inhibitors, checkpoint inhibitors, and chemotherapy) in various treatment settings, including frontline protocols. An extended half-life BiTE molecule is also under investigation. Patients receiving blinatumomab may experience cytokine release syndrome and neurotoxicity; however, these events may be less frequent and severe than in patients receiving other CD19-targeted immunotherapies, such as chimeric antigen receptor T cell therapy. We review BiTE technology for treating malignancies that express CD19, analyzing the benefits and limitations of this bispecific T cell engager platform from clinical experience with blinatumomab.

Model of Short- and Long-Term Outcomes of Emicizumab Prophylaxis Treatment for Persons with Hemophilia A.

BACKGROUND: Hemophilia A (HA) can result in bleeding events because of low or absent clotting factor VIII (FVIII). Prophylactic treatment for severe HA includes replacement FVIII infusions and emicizumab, a bispecific factor IXa- and factor X-directed antibody. OBJECTIVE: To develop an economic model to predict the short- and long-term clinical and economic outcomes of prophylaxis with emicizumab versus short-acting recombinant FVIII among persons with HA in the United States. METHODS: A Markov model was developed to compare clinical outcomes and costs of emicizumab versus FVIII prophylaxis among persons with severe HA from U.S. payer and societal perspectives. Patients started prophylaxis at age 1 year in the base case. Mutually exclusive health states considered were "no arthropathy," "arthropathy," "surgery," and "death." Serious adverse events, breakthrough bleeds, and inhibitor development were simulated throughout the modeled time horizon. In addition to the prophylaxis drug costs, patients could incur other direct costs related to breakthrough bleeds treatment, serious adverse events, development of inhibitors, arthropathy, and orthopedic surgery. Indirect costs associated with productivity loss (i.e., missed work or disabilities) were applied for adults. Model inputs were obtained from the HAVEN 3 trial, published literature, and expert opinion. The model used a lifetime horizon, and results for 1 year and 5 years were also reported. Deterministic sensitivity analyses and scenario analyses were conducted to assess robustness of the model. RESULTS: Over a lifetime horizon, the cumulative number of all treated bleeds and joint bleeds avoided on emicizumab versus FVIII prophylaxis were 278.2 and 151.7, respectively. Correspondingly, arthropathy (mean age at onset: 12.9 vs. 5.4 years) and FVIII inhibitor development (mean age at development: 13.9 vs. 1.1 years) were delayed. Total direct and indirect costs were lower for emicizumab versus FVIII prophylaxis for all modeled time horizons ($97,159 vs. $331,610 at 1 year; $603,146 vs. $1,459,496 at 5 years; and $15,238,072 vs. $22,820,281 over a lifetime horizon). The sensitivity analyses indicated that clinical outcomes were sensitive to efficacy inputs, while economic outcomes were driven by the discount rate, dosing schedules, and treatments after inhibitor development. Results for moderate to severe patients were consistent with findings in the severe HA population. CONCLUSIONS: The model suggests that emicizumab prophylaxis confers additional clinical benefits, resulting in a lower number of bleeding events and delayed onset of arthropathy and inhibitor development across all time assessment horizons. Compared with short-acting recombinant FVIII, emicizumab prophylaxis leads to superior patient outcomes and cost savings from U.S. payer and societal perspectives. DISCLOSURES: Funding for this study was provided by Genentech. Raimundo and Patel are employees of Genentech and own stock or stock options. Zhou, Han, Ji, Fang, Zhong, and Betts are employees of Analysis Group, which received consultancy fees from Genentech for conducting this study. Mahajerin received consultancy fees from Genentech for work on this study. Portions of this research were presented as a poster at the 2018 American Society of Hematology Conference; December 1-4, 2018; San Diego, CA.

Cost-Effectiveness and Budget Impact of Emicizumab Prophylaxis in Haemophilia A Patients with Inhibitors.

Recent evidence demonstrated that weekly prophylaxis with subcutaneous bispecific antibody (emicizumab) has shown higher efficacy in adolescent and adults patients affected by haemophilia A (HA) with inhibitor, compared with patients treated on demand or on prophylaxis with bypassing agents (BPAs). However, no economic evaluations assessing the value and sustainability of emicizumab prophylaxis have been performed in Europe. This study assessed the cost-effectiveness of emicizumab prophylaxis compared with BPA prophylaxis and its possible budget impact from the Italian National Health Service (NHS) perspective. A Markov model and a budget impact model were developed to estimate the cost-effectiveness and budget impact of emicizumab prophylaxis in HA patients with inhibitors. The model was populated using treatment efficacy from clinical trials and key clinical, cost and epidemiological data retrieved through an extensive literature review. Compared with BPAs prophylaxis, emicizumab prophylaxis was found to be more effective (0.94 quality adjusted life-years) and cost saving (-€19.4/-€24.4 million per patient lifetime) in a cohort of 4-year-old patients with HA and inhibitors who failed immune tolerance induction. In the probabilistic sensitivity analysis, emicizumab prophylaxis had always 100% probability of being cost-effective at any threshold. Further, the use of emicizumab prophylaxis was associated to an overall budget reduction of €45.4 million in the next 3 years. In conclusion, the clinically effective emicizumab prophylaxis can be considered a cost-saving treatment for HA with inhibitor patients. Furthermore, emicizumab treatment is also associated to a significant reduction of the health care budget, making this new treatment a sustainable and convenient health care option for Italian NHS.

Economic impact model of delayed inhibitor development in patients with hemophilia a receiving emicizumab for the prevention of bleeding events.

Aims: Cumulative exogenous factor VIII (FVIII) exposure is an important predictor of developing neutralizing antibodies (inhibitors) to FVIII in patients with persons with hemophilia A (PwHA). The aim of this study was to model the costs of emicizumab versus FVIII prophylaxis and total treatment costs for patients with severe HA.Materials and Methods: An Excel-based decision model was developed to calculate cumulative costs in PwHA over a 20-year time horizon from the US payer perspective. The model considered persons with severe HA beginning at age 12 months with no prior FVIII exposure and initiating prophylaxis with emicizumab or FVIII. PwHA could develop inhibitors on accumulation of 20 FVIII exposure days. PwHA with inhibitors replaced FVIII with bypassing agents until inhibitors resolved spontaneously, following immune tolerance induction (ITI), or at the end of the time horizon. The primary model outcome was the difference in emicizumab versus FVIII treatment costs in 2019 USD. Sensitivity analyses were performed to test the robustness of results.Results: Total incremental cost over 20 years was -$1,945,480 (emicizumab arm, $4,919,058; FVIII arm, $6,864,538). Prophylaxis costs (emicizumab arm, $4,096,105; FVIII arm, $6,290,919) comprised the majority of costs in both groups, followed by breakthrough bleed treatment for the FVIII arm ($342,652) and ITI costs for the emicizumab arm ($733,671). Higher costs in the FVIII group reflected earlier inhibitor development (FVIII, 4 months; emicizumab, 162 months) and switch to bypassing agents.Limitations: The model design reflects a simplified treatment pathway for patients with severe HA who initiate FVIII or emicizumab prophylaxis. In the absence of clinical data, a key conservative assumption of the model is that patients receiving emicizumab and FVIII prophylaxis have the same risk of developing inhibitors.Conclusions: This study suggests that prophylaxis with emicizumab results in cost savings compared to FVIII prophylaxis in HA.

Cost Effectiveness of Blinatumomab Versus Inotuzumab Ozogamicin in Adult Patients with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia in the United States.

BACKGROUND AND OBJECTIVE: The TOWER and INO-VATE-ALL trials demonstrated the efficacy and safety of blinatumomab and inotuzumab ozogamicin (inotuzumab), respectively, versus standard-of-care (SOC) chemotherapy in adults with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). The cost effectiveness of blinatumomab versus inotuzumab has not previously been examined. METHODS: Cost effectiveness of blinatumomab versus inotuzumab in R/R B-cell precursor ALL patients with one or no prior salvage therapy from a United States (US) payer perspective was estimated using a partitioned survival model. Health outcomes were estimated based on published aggregate data from INO-VATE-ALL and individual patient data from TOWER weighted to match patients in INO-VATE-ALL using matching adjusted indirect comparison (MAIC). Analyses were conducted using five approaches relating to use of anchored versus unanchored comparisons of health outcomes and, for the anchored comparisons, the reference treatment to which treatment effects on health outcomes were applied. Estimates from TOWER including the probabilities of complete remission and allogeneic stem-cell transplant (allo-SCT), overall and event-free survival, utilities, duration of therapy, and use of subsequent therapies were MAIC adjusted to match INO-VATE-ALL. Costs of treatment, adverse events, allo-SCT, subsequent therapies, and terminal care were from published sources. A 50-year time horizon and 3% annual discount rate were used. RESULTS: Incremental costs for blinatumomab versus inotuzumab ranged from US$7023 to US$36,244, depending on the approach used for estimating relative effectiveness. Incremental quality-adjusted life-years (QALYs) ranged from 0.54 to 1.78. Cost effectiveness for blinatumomab versus inotuzumab ranged from US$4006 to US$20,737 per QALY gained. CONCLUSIONS: Blinatumomab is estimated to be cost effective versus inotuzumab in R/R B-cell precursor ALL adults who have received one or no prior salvage therapy from a US payer perspective.

No free rides: management of toxicities of novel immunotherapies in ALL, including financial.

Therapeutic options for acute lymphoblastic leukemia, especially in the relapsed/refractory setting, have expanded significantly in recent times. However, this comes at the cost of toxicities: medical as well as financial. We highlight some of the unique toxicities associated with the novel agents to apprise our readers about what to expect, how to recognize them, and how to manage these toxicities. One of the toxicities seen with inotuzumab, a CD22 antibody drug conjugate, is sinusoidal obstruction syndrome, which can be fatal in >80% of patients if associated with multiorgan failure. Blinatumomab, a monoclonal antibody targeting CD19, is associated with cytokine release syndrome (CRS) and neurotoxicity, both of which require prompt recognition and management primarily with corticosteroids. CRS and neurotoxicity are more common and more severe with chimeric antigen receptor T-cell therapy (CAR-T). The fact that CAR-T cannot be discontinued on demand adds a layer of complexity to the management of related toxicities of this therapy. Tocilizumab, an interleukin-6 receptor blocker, is used to treat severe CRS from CAR-T, whereas corticosteroids remain the mainstay for neurotoxicity management. Although effective, these drugs carry a high price tag, and we review the available data on cost-effectiveness of these agents, keeping in mind that median follow-up on most of these studies is limited and that long-term data on durability of response remain to be seen.

Cost-effectiveness of blinatumomab versus salvage chemotherapy in relapsed or refractory Philadelphia-chromosome-negative B-precursor acute lymphoblastic leukemia from a US payer perspective.

OBJECTIVE: To evaluate the cost-effectiveness of blinatumomab (Blincyto) vs standard of care (SOC) chemotherapy in adults with relapsed or refractory (R/R) Philadelphia-chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL) based on the results of the phase 3 TOWER study from a US healthcare payer perspective. METHODS: The Blincyto Global Economic Model (B-GEM), a partitioned survival model, was used to estimate the incremental cost-effectiveness ratio (ICER) of blinatumomab vs SOC. Response rates, event-free survival (EFS), overall survival (OS), numbers of cycles of blinatumomab and SOC, and transplant rates were estimated from TOWER. EFS and OS were estimated by fitting parametric survival distributions to failure-time data from TOWER. Utility values were based on EORTC-8D derived from EORTC QLQ-C30 assessments in TOWER. A 50-year lifetime horizon and US payer perspective were employed. Costs and outcomes were discounted at 3% per year. RESULTS: The B-GEM projected blinatumomab to yield 1.92 additional life years and 1.64 additional quality-adjusted life years (QALYs) compared with SOC at an incremental cost of $180,642. The ICER for blinatumomab vs SOC was estimated to be $110,108/QALY gained in the base case. Cost-effectiveness was sensitive to the number and cost of inpatient days for administration of blinatumomab and SOC, and was more favorable in the sub-group of patients who had received no prior salvage therapy. At an ICER threshold of $150,000/QALY gained, the probability that blinatumomab is cost-effective was estimated to be 74%. LIMITATIONS: The study does not explicitly consider the impact of adverse events of the treatment; no adjustments for long-term transplant rates were made. CONCLUSIONS: Compared with SOC, blinatumomab is a cost-effective treatment option for adults with R/R Ph - B-precursor ALL from the US healthcare perspective at an ICER threshold of $150,000 per QALY gained. The value of blinatumomab is derived from its incremental survival and health-related quality-of-life (HRQoL) benefit over SOC.

Blinatumomab: a CD19/CD3 bispecific T cell engager (BiTE) with unique anti-tumor efficacy.

Blinatumomab is a member of a novel class of T cell-engaging bispecific antibodies, so-called Bispecific T cell Engager (BiTEs). It is directed against the B cell differentiation antigen CD19 and intended for treatment of B cell malignancies. In clinical phase I/II trials, blinatumomab showed remarkable single-agent activity in patients with relapsed and/or refractory (R/R) non-Hodgkin lymphoma and R/R B cell precursor acute lymphoblastic leukemia (B-precursor ALL). Cytokine release syndrome and neurological side effects were dose-limiting. Adverse effects were well manageable and transient in nature. Based on results of an international phase II trial, blinatumomab received FDA approval for the treatment of R/R B-precursor ALL in December 2014. Ongoing and future trials will contribute to further optimization of blinatumomab-based T cell therapy and have to show that integration of blinatumomab in current and innovative treatment protocols improves overall survival and quality of life of patients with B cell malignancies.