Cost-Effectiveness of Blinatumomab Versus Standard of Care in Adult Patients with Philadelphia-Chromosome-Negative B-Precursor Acute Lymphoblastic Leukemia in First Hematological Complete Remission (CR) with Minimal Residual Disease (MRD) from a US Payer Perspective

Abstract INTRODUCTION: Blinatumomab is a bispecific CD19 directed CD3 T cell engager indicated for the treatment of adults and children with B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission (CR) with minimal residual disease (MRD) greater than or equal to 0.1%. In BLAST (NCT01207388), an open-label, multicenter, single-arm, phase 2 study of blinatumomab in patients with MRD positive B-precursor ALL in hematological CR, blinatumomab resulted in complete MRD response in cycle 1 in 78% of patients. Overall survival (OS) was significantly better in those with MRD vs those without MRD. The objective of this study is to evaluate the cost-effectiveness of blinatumomab vs. standard of care (SOC) therapy in patients with Ph- B-cell precursor ALL in first hematological CR with MRD based on the BLAST study from a US healthcare payer perspective. METHODS: A partitioned survival model was used to estimate the incremental cost-effectiveness ratio (ICER) of blinatumomab vs. SOC maintenance. A 50-year lifetime horizon and US payer perspective were employed. Costs and outcomes were discounted at 3% annually. Probabilities of complete MRD response, relapse-free survival (RFS), OS, numbers of cycles of blinatumomab and SOC, and transplant rates were estimated from BLAST and a historical cohort comparator study using propensity score analyses. RFS and OS were based on parametric survival distributions fit to individual patient failure-time data. Utility values were based from a generalized linear model/generalized estimating equation (GLM/GEE) model fitted to EQ-5D data collected in BLAST applying US tariffs. Inpatient and outpatient healthcare use by MRD status was from an observational study which evaluated treatment patterns and healthcare resource utilization in adult B-cell precursor ALL in first hematological CR with and without MRD. Deterministic and probabilistic sensitivity analyses were conducted to assess the effects of changes in model assumptions and uncertainty around key parameters. RESULTS: The unrestricted Gompertz distribution for RFS and lognormal mixture cure model distribution for OS were selected. In the base case, blinatumomab was projected to yield 3.52 additional life years and 2.93 additional quality-adjusted life years (QALYs) compared with SOC. Blinatumomab is associated with higher drug and administration costs and transplant costs, which were partially offset by lower post-relapse costs. The ICER for blinatumomab vs. SOC maintenance therapy was estimated to be $81,807/QALY gained (table). The main cost drivers were the drug acquisition costs and the additional hematopoietic stem cell transplant costs with blinatumomab. Cost-effectiveness was mostly sensitive to the uncertainty around the cure fraction (proportion of patients whose survival pattern is similar to the general cancer-free population) and transplant rates. Assumptions that most affected cost-effectiveness were the duration of benefit of blinatumomab and the long-term mortality estimation. The cost-effectiveness remained below the willingness-to-pay threshold value of $150,000/QALY gained in all scenarios tested. In the probabilistic sensitivity analyses, the estimated probability that blinatumomab is cost-effective was 87% at a willingness-to-pay threshold of $150,000/QALY. CONCLUSIONS: Blinatumomab is a cost effective treatment option vs. SOC for adults with Ph - B-precursor ALL in first hematological CR with MRD from the US healthcare perspective with an ICER well below the threshold of $150,000 per QALY gained. The value of blinatumomab is derived from its high complete MRD response rate, prolonged RFS, and OS. Disclosures Delea: Seattle Genetics: Research Funding; Takeda: Research Funding; Sanofi: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Policy Analysis Inc.: Employment. Despiegel:Amgen, Inc.: Employment, Equity Ownership. Boyko:Amgen: Research Funding. Amdahl:Amgen: Research Funding. Cong:Amgen, Inc.: Employment, Equity Ownership.

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Cost Effectiveness Analysis of Venetoclax Plus Azacitidine Versus Azacitidine in Newly Diagnosed Adult Patients with Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy from a United States Payer Perspective

Blood ◽

10.1182/blood-2021-148338 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 112-112

Author(s):

Keith W. Pratz ◽

Xinglei Chai ◽

Jipan Xie ◽

Lei Yin ◽

Xiaoyu Nie ◽

...

Keyword(s):

Cost Effectiveness ◽

Research Funding ◽

Time Horizon ◽

Cost Effective ◽

Sensitivity Analyses ◽

Base Case ◽

Intensive Chemotherapy ◽

Publicly Traded ◽

Analysis Group ◽

Payer Perspective

Abstract Background: The phase 3 VIALE-A trial (NCT02993523) demonstrated that venetoclax plus azacitidine (VEN+AZA) improved overall survival (OS) and led to higher remission rates compared with AZA monotherapy, in patients with newly diagnosed (ND) acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. Based on the results from VIALE-A, VEN+AZA received full United States (US) Food and Drug Administration approval in October 2020 for patients with ND AML aged ≥75 years, or who were ineligible for intensive induction chemotherapy due to comorbidities. This study aims to assess the long-term cost-effectiveness value of the VEN+AZA regimen from the VIALE-A trial from a US third-party payer perspective. Methods: A partitioned survival model with a 28-day cycle was developed to estimate costs and outcomes of treatment with VEN+AZA vs. AZA among patients with ND AML, who are ineligible for intensive chemotherapy, over a lifetime time horizon. The model included three health states: event-free survival (EFS), progressive/relapsed disease, and death. Within the EFS state, patients were further partitioned into time spent in complete remission (CR) or CR with incomplete marrow recovery (CRi), and time spent in non-CR/CRi. Efficacy inputs (OS, EFS, and CR/CRi rate) for both treatment arms were estimated using VIALE-A data. Best-fit parametric models per Akaike information criterion (AIC) were used to extrapolate OS until it reached EFS, and extrapolate EFS for each treatment until Year 5. Patients who remained in EFS after Year 5 were considered cured, and were assumed to have the same mortality as the US general population. Mean time on treatment (ToT) for both regimens was based on the time observed in VIALE-A. The costs for drug acquisition, drug administration for initial and subsequent treatments, subsequent stem cell transplant procedures, adverse events (AEs), and healthcare resource utilization (HRU) associated with each health state were obtained from the literature or publicly available data. All costs were inflated to 2021 US dollars. Utilities for each health state were estimated using EuroQol-5 dimension-5 level (EQ-5D-5L) data from VIALE-A, based on the US crosswalk value set. Information on disutilities due to Grade 3/4 AEs were obtained from the literature. Incremental cost-effectiveness ratios (ICERs) per life year (LY) and quality-adjusted life year (QALY) gained were estimated. Deterministic sensitivity analyses (DSA), scenario analyses and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the results. Results: Over a lifetime time horizon, compared with AZA, VEN+AZA was associated with an increase of 1.89 LYs (1.10 vs. 2.99, respectively) and 1.45 QALYs (0.84 vs. 2.30, respectively). Patients in the VEN+AZA arm incurred higher total costs ($250,486 vs. $110,034 for patients in the AZA arm). The ICER for VEN+AZA vs. AZA was estimated to be $74,141 per LY gained, and $96,579 per QALY gained. Results from the DSA and scenario analyses supported the base-case findings, with ICERs ranging from $60,922 to $138,554 per QALY gained. The results were most sensitive to alternative approaches for ToT estimation, subsequent treatment HRU costs, cure time point, and the extrapolation approach for EFS. Results from PSA showed that compared with AZA, VEN+AZA was cost-effective in 99.9% of cases at a willingness-to-pay (WTP) threshold of $150,000. Conclusions: Compared with AZA monotherapy, VEN+AZA results in a favorable ICER of $96,579 per QALY gained over a lifetime time horizon. The base-case results suggest that, compared with AZA, VEN+AZA is a cost-effective strategy based on a WTP threshold of $150,000 per QALY gained. Sensitivity analyses support the base-case results. Thus, VEN+AZA offers a cost-effective strategy in the treatment of patients with ND AML who are ineligible for intensive chemotherapy from a US third-party payer perspective. Disclosures Pratz: Agios: Consultancy; Abbvie: Consultancy, Honoraria, Research Funding; University of Pennsylvania: Current Employment; BMS: Consultancy, Honoraria; Novartis: Consultancy; Astellas: Consultancy, Honoraria, Research Funding; Cellgene: Consultancy, Honoraria; Millenium: Research Funding. Chai: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Yin: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Nie: Analysis Group, Inc.: Consultancy, Current Employment; Genentech, Inc.: Consultancy. Montez: Genentech, Inc: Current Employment, Other: May hold equity. Iantuono: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Downs: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Ma: Genentech, Inc.: Current Employment, Other: May hold equity.

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Switching Towards Monocytic Lineage and Discordancy between Flow Cytometric and PCR Minimal Residual Disease Results Is a Hallmark Feature of DUX4 Rearranged B-Cell Precursor Acute Lymphoblastic Leukemia

Blood ◽

10.1182/blood-2018-99-116575 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2825-2825

Author(s):

Michaela Novakova ◽

Barbora Vakrmanova ◽

Lucie Slamova ◽

Alena Musilova ◽

Monika Brüggemann ◽

...

Keyword(s):

B Cell ◽

Treatment Response ◽

Research Funding ◽

Residual Disease ◽

Lymphoblastic Leukemia ◽

Response To Treatment ◽

Cell Precursor ◽

Treatment Protocols ◽

Monocytic Lineage ◽

Minimal Residual

Abstract Introduction: Recently we described a subgroup of pediatric patients with B cell precursor acute lymphoblastic leukemia (BCP ALL) with switching from B to monocytic lineage in early phase of the therapy (Slamova et al., 2014). In a limited cohort of patients with switching ALL (swALL), we observed inferior response to treatment with discrepancy of minimal residual disease level (MRD) assessed by flow cytometry (FC) and quantitative polymerase chain reaction (qPCR) of Immunoglobulin-T cell receptor (Ig-TCR) rearrangements. In current Berlin-Frankfurt-Münster (BFM) treatment protocols, FC MRD value at day 15 (d15) and PCR MRD value at day 33 (d33) and week 12 (w12) are used for stratification. Using an extended cohort of patients with available RNA sequencing data (cohort mainly focused on B other cases or swALLs) we aimed to answer following questions:What is the genetic background of swALL? What is the frequency among swALLs of the recently described DUX4 rearranged subgroup?How do B cell oriented FC and PCR MRD correlate in standard protocol timepoints, i.e. day 8 (d8) (peripheral blood, PB) d15, d33 and w12 (bone marrow, BM) of treatment?What is the characteristic MRD response to treatment in swALL? Results:We performed RNA sequencing in 177 patients (median age 6.1 years, range 0-18) treated by several treatment protocols (ALL BFM 95 n=5, ALL IC BFM 2002 n=14, ALL AIEOP BFM 2000 n=17, ALL AIEOP BFM 2009 n=135, Interfant n=3, ALL IC/Interfant n=2, EsPhALL n=1). In 68 patients we observed switching phenomenon by appearance of B/monocytoid population coexpressing B lineage (CD19, CD34) and monocytic lineage (CD33, CD14) markers (median 0.98%, range 0.032-38%). In non swALLs median of this population was 0.059% (range 0.0025-1.1%) and the cells did not form a clear cluster. According to RNAseq data, majority of swALL patients (n=42/68) belong to DUX4 subgroup (chi square p< 0.00001). The distribution into other molecular genetic subtypes is summarized in table 1.Correlation coefficient (Spearman) of all included samples with both available values (n=552) was 0.82 (p<0.0001), Concordance in categorization of positivity and negativity with cut-off 1e-4 was 85%. We observed worse correlation between FC and PCR MRD in patients with swALL (d8 R=0.58, d15 R=0.6, d33 R=0.36, w12 n.s.) compared to non swALL (d8 R=0.83, d15 R=0.91, d33 R=0.69, w12 R=0.37). However, concordance in swALL in categorization of positivity and negativity with cut-off 1e-4 was still ≥80% in each analyzed timepoint apart from d33 with concordance only 44% showing significant discrepancy of both methods (Figure 1a). On the contrary, concordance in non swALL was ≥87% for each analyzed timepoint (d33 with concordance 87% shown in Figure 1b). Poor correlation between B-cell oriented FC MRD and PCR MRD at d33 was also obvious when analyzed DUX4 subgroup separately (R=0.31 (p=0.04), concordance 45%).We observed significantly higher MRD in swALLs compared to non swALLs at all analyzed timepoints: d8 (p=0.0021), d15 (p=0.0088, d33 (p<0.0001) and w12 (p=0.008). Higher MRD levels were also found in DUX4 patients when compared to non DUX4 (all timepoints p<0.05). Interestingly, when compared swALL and non swALLs pts in DUX4 subgroup only, the DUX4 swALLs are those with poorer treatment response (all timepoints p<0.05). With respect to protocolar cut-off values, FC MRD at d15 was above 10% in 18/67 swALL patients (in 13/52 DUX4 patients), d33 PCR MRD was above 0.1% in 33/57 swALLs (24/44 DUX4 pts) and at w12 PCR MRD was above 0.01% in 12/55 swALLs (10/44 DUX4 pts). Conclusions: DUX4 subgroup is the most prevalent genetic subtype among swALLs. SwALLs and/or DUX4 subgroup have poorer treatment response at d15, d33 and w12. However, it remains to be elucidated whether poor initial treatment response is eventually reflected in treatment outcome. In majority of swALL patients B cell phenotype of blasts is preserved at day 15 enabling correct classification. Prominent discrepancy between FC and PCR MRD is present especially at d33 and development of different FC MRD strategies focused on monocytic compartment is needed. Supported by Ministry of Health of the Czech Republic, grant nr. 15-28525A and NV18-03-00343; Czech Science Foundation nr. P302/12/G101, UNCE204012 Disclosures Brüggemann: Affimed: Research Funding; Regeneron: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Roche: Speakers Bureau; Pfizer: Speakers Bureau; Incyte: Consultancy; PRMA: Consultancy. Ritgen:abbvie: Research Funding; Roche: Honoraria, Research Funding.

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Health-Related Quality of Life in Adults with B-Cell Precursor Acute Lymphoblastic Leukemia and Minimal Residual Disease Treated with Blinatumomab

Blood ◽

10.1182/blood-2018-99-112259 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1377-1377 ◽

Cited By ~ 1

Author(s):

Ralf C Bargou ◽

Gerhard Zugmaier ◽

Massimiliano Bonifacio ◽

Carlos Graux ◽

Christoph Faul ◽

...

Keyword(s):

Health Status ◽

Global Health ◽

B Cell ◽

Social Functioning ◽

Research Funding ◽

Residual Disease ◽

Lymphoblastic Leukemia ◽

Global Health Status ◽

Cell Precursor ◽

Support Research

Abstract Background: Positive minimal residual disease (MRD) is an established prognostic marker for hematologic relapse, negative hematopoietic stem cell transplantation (HSCT) outcome, and mortality in adults with B-cell precursor acute lymphoblastic leukemia (ALL; Gökbuget N, et al. Blood. 2012;120:1868-1876). In the open-label, single-arm phase 2 BLAST study (N=116; ClinicalTrials.gov, NCT01207388), treatment with blinatumomab, a bispecific T-cell engager (BiTE®) antibody construct that redirects cytotoxic T cells to residual CD19+ blast cells, led to complete MRD response in 88 of 113 (78%) patients after cycle 1 (Gökbuget N, et al. Blood. 2018;131:1522-1531). Median overall survival was 36.5 months. Among patients with Philadelphia chromosome-negative B-cell ALL in complete MRD remission, relapse-free survival was 54% at 18months. In this analysis of the BLAST study, we assessed the health-related quality of life (HRQoL) of patients during and after treatment with blinatumomab. Methods: Eligible patients (≥18 years) had B-cell precursor ALL in first or later hematologic complete remission and persistent or recurrent MRD ≥10-3 after ≥3 blocks of intensive chemotherapy. Blinatumomab 15 μg/m2/day was administered by continuous intravenous (cIV) infusion for 4 weeks, followed by a 2-week infusion-free interval, for up to 4 cycles. Patients could receive HSCT any time after cycle 1. HRQoL was assessed using the EORTC QLQ-C30 Questionnaire at baseline, on day 29 of each treatment cycle, at the safety follow-up visit (30 days after end of treatment), and at the efficacy follow-up visits (3, 6, 9, 12, 18, and 24 months after treatment start). The questionnaire included 1 global health status scale, 5 functioning scales (physical, role, emotional, cognitive, and social functioning), 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single-symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). For global health status and functioning scales, a higher score indicates better HRQoL; for symptom scales/items, a lower score indicates better HRQoL. A 10-point change is often viewed as the minimum clinically important difference (MID) in EORTC QLQ-C30 (Zikos E, et al. EORTC, 2016). In this analysis, the mean (SD) and the mean (SD) change from baseline to end of cycle 1 of the scores for each scale/item was summarized at each scheduled assessment during and after blinatumomab treatment. Results: In total, 89 patients had a nonmissing baseline value and a nonmissing value of any scale on day 29 of cycle 1, and thus were evaluable for HRQoL. The patient-reported global health status and functioning scale scores were stable over time during and after blinatumomab treatment (Figure 1). Symptom-scale and single-symptom scores were similarly stable during and after treatment (not shown). Mean (SD) changes from baseline to end of cycle 1 in global health status and in physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning were 2.5 (18.5), 0.3 (12.5), -4.0 (30.0), 4.2 (20.5), -1.7 (16.2), and 10.4 (31.8), respectively (Figure 2). These results show that, after 1 cycle of blinatumomab, the change in HRQoL was minimal for most scales, with potential clinically meaningful improvements in social functioning. Similar minimal changes were observed for all symptom scales/items (not shown). Conclusions: In this population of patients with B-cell precursor ALL and MRD successfully treated with blinatumomab 15 μg/m2/day cIV for up to 4 cycles, HRQoL was maintained during and after blinatumomab treatment, which is an important result considering the potential HRQoL impact of standard chemotherapy. Disclosures Zugmaier: Amgen Inc.: Consultancy, Employment, Patents & Royalties: 20170327581, 9688760, 20170122947, 9486475, 20160208001, 9192665, 20150071928, 8840888, 20140227272, 20140228316, 20130323247, 20130287774, 20130287778, 20110262440, 20100112603, 7700299, 20070037228. Bonifacio:Incyte: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; Novartis: Research Funding; Bristol Myers Squibb: Consultancy. Topp:Boehringer Ingelheim: Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding. Tran:Amgen Inc.: Employment. Zhang:Amgen Inc.: Employment, Equity Ownership. Goekbuget:Kite / Gilead: Consultancy; Celgene: Consultancy; Novartis: Consultancy, Other: Travel support, Research Funding; Pfizer: Consultancy, Other: Travel support, Research Funding; Amgen: Consultancy, Other: Travel support, Research Funding.

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Atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma: A cost-effectiveness analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.295 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 295-295 ◽

Cited By ~ 1

Author(s):

Wenjun Wang ◽

Jingjing Wang ◽

Xin Zhang ◽

Yikai Wang ◽

Juanjuan Shi ◽

...

Keyword(s):

Cost Effectiveness ◽

Cost Effective ◽

Sensitivity Analyses ◽

First Line ◽

Payer Perspective ◽

Life Years ◽

The Us ◽

Subgroup Analyses ◽

Metastatic Hepatocellular Carcinoma ◽

First Line Treatment

295 Background: In May 2020, atezolizumab plus bevacizumab was approved by US Food and Drug Administration for patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy due to improvement in overall and progression-free survival compared with standard sorafenib treatment. However, because of the high cost of atezolizumab plus bevacizumab, there is a need to assess its value by considering both efficacy and cost. The aim of this study is to evaluate the cost-effectiveness of atezolizumab plus bevacizumab vs sorafenib for patients with unresectable or metastatic HCC from the US payer perspective. Methods: A partitioned-survival model was developed to compare health care costs and clinical outcomes of atezolizumab plus bevacizumab vs sorafenib in first-line treatment of unresectable or metastatic HCC over 6-year horizon. Treatment effects were extracted from the IMbrave150 trial. Health care cost and health utility data were obtained from published studies and databases. Incremental cost-effectiveness ratio (ICER) was calculated as the ratio of the incremental cost to the incremental quality-adjusted life years (QALYs). One-way deterministic and probabilistic sensitivity analyses were used to examine model uncertainty. Additional subgroup analyses were performed. Results: Atezolizumab plus bevacizumab resulted in increase of 0.623 life-years, 0.484 QALYs and $158,781 per patient at the base case analysis. The ICER was $322,500 per QALY (95% confidence interval, $136,275 to $801,509 per QALY), with 0.5% and 4.1% chance of being cost-effective at a willingness-to-pay threshold of $100,000 and $150,000 per QALY, respectively. The ICER never went below $150,000 per QALY in the one-way sensitivity analyses and among patients of clinically relevant subgroups in the subgroup analyses. Conclusions: Atezolizumab plus bevacizumab is unlikely to be cost-effective compared with sorafenib in first-line treatment of patients with unresectable or metastatic HCC from the US payer perspective.

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Cost-effectiveness of FOLFIRI + cetuximab vs FOLFIRI + bevacizumab in the first-line (1L) treatment of RAS wild-type (wt) metastatic colorectal cancer (mCRC) in Germany: Data from the FIRE-3 (AIO KRK-0306) study.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.800 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 800-800 ◽

Cited By ~ 1

Author(s):

Sebastian Stintzing ◽

Ilse van Oostrum ◽

Chris Pescott ◽

Alma Katharina Steinbach-Buechert ◽

Bart Heeg ◽

...

Keyword(s):

Cost Effectiveness ◽

Cost Effective ◽

Cost Utility ◽

Sensitivity Analyses ◽

Base Case ◽

Health State ◽

Primary Tumors ◽

Payer Perspective ◽

Life Years ◽

The Cost

800 Background: The randomized, phase 3 FIRE-3 trial evaluated 1L FOLFIRI + cetuximab or bevacizumab in patients with RAS wt mCRC; overall survival favored FOLFIRI + cetuximab by > 8 months. The purpose of this analysis was to evaluate the cost-effectiveness of FOLFIRI + cetuximab vs that of FOLFIRI + bevacizumab as 1L treatment for patients in Germany with RAS wt mCRC (including the patient subgroup with RAS wt, left-sided [LS] primary tumors, as LS is a predictive factor). Methods: A standard oncology 3–health-state partitioned survival cost-utility model was developed to analyze the costs and health benefits of FOLFIRI + cetuximab vs those of FOLFIRI + bevacizumab from a German payer perspective based on data from FIRE-3 and the literature. Health outcomes were reported in life-years (LYs) and quality-adjusted life-years (QALYs) gained. A 3.5% discounting rate was applied to the modeled costs and outcomes. Results: Discounted costs, health gains, and incremental cost-effectiveness ratios (ICERs) for patients with RAS wt (base case) and patients with RAS wt, LS (subgroup) mCRC are summarized in the Table. Probabilistic sensitivity analyses showed that at relevant European willingness-to-pay (WTP) thresholds of €55,000 and €80,000, FOLFIRI + cetuximab had a 64.0% and 81.6% (base case) and 80.5% and 92.4% (subgroup) probability of being cost-effective vs FOLFIRI + bevacizumab, respectively. Clinical trial information: NCT00433927. Conclusions: Based on our analyses, FOLFIRI + cetuximab is cost-effective compared with FOLFIRI + bevacizumab in patients in Germany with RAS wt mCRC at official WTP thresholds applied by relevant European health technology assessment agencies. The cost-effectiveness of FOLFIRI + cetuximab is more pronounced in the subgroup of patients with RAS wt, LS tumors.[Table: see text]

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First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

Cancers ◽

10.3390/cancers13050931 ◽

2021 ◽

Vol 13 (5) ◽

pp. 931

Author(s):

Chi-Leung Chiang ◽

Sik-Kwan Chan ◽

Shing-Fung Lee ◽

Horace Cheuk-Wai Choi

Keyword(s):

Hepatocellular Carcinoma ◽

Cost Effectiveness ◽

Lifetime Cost ◽

Cost Effective ◽

First Line ◽

First Line Therapy ◽

Payer Perspective ◽

Life Years ◽

Using Data

Background: The IMbrave 150 trial revealed that atezolizumab plus bevacizumab (atezo–bev) improves survival in patients with unresectable hepatocellular carcinoma (HCC) (1 year survival rate: 67.2% vs. 54.6%). We assessed the cost-effectiveness of atezo–bev vs. sorafenib as first-line therapy in patients with unresectable HCC from the US payer perspective. Methods: Using data from the IMbrave 150, we developed a Markov model to compare the lifetime cost and efficacy of atezo–bev as first-line systemic therapy in HCC with those of sorafenib. The main outcomes were life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Results: Atezo–bev demonstrated a gain of 0.44 QALYs, with an additional cost of USD 79,074. The ICER of atezo–bev was USD 179,729 per QALY when compared with sorafenib. The model was most sensitive to the overall survival hazard ratio and body weight. If we assumed that all patients at the end of the IMbrave 150 trial were cured of HCC, atezo–bev was cost-effective (ICER USD 53,854 per QALY). However, if all patients followed the Surveillance, Epidemiology, and End Results data, the ICER of atezo–bev was USD 385,857 per QALY. Reducing the price of atezo–bev by 20% and 29% would satisfy the USD 150,000/QALY and 100,000/QALY willingness-to-pay threshold. Moreover, capping the duration of therapy to ≤12 months or reducing the dosage of bev to ≤10 mg/kg would render atezo–bev cost-effective. Conclusions: The long-term effectiveness of atezo–bev is a critical but uncertain determinant of its cost-effectiveness. Price reduction would favorably influence cost-effectiveness, even if long-term clinical outcomes were modest. Further studies to optimize the duration and dosage of therapy are warranted.

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Ixazomib (IXA), carfilzomib (CAR), elotuzumab (ELO) or daratumumab (DAR) with lenalidomide and dexamethasone (LEN+DEX) versus LEN+DEX only in relapsed/refractory multiple myeloma (R/R MM): A comparative cost-effectiveness analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8043 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8043-8043

Author(s):

Mavis Obeng-Kusi ◽

Daniel Arku ◽

Neda Alrawashdh ◽

Briana Choi ◽

Nimer S. Alkhatib ◽

...

Keyword(s):

Cost Effectiveness ◽

Cost Effective ◽

Cost Utility ◽

Cost Effectiveness Analysis ◽

The Other ◽

Sensitivity Analyses ◽

Treatment Comparison ◽

Comparative Cost ◽

Effectiveness Analysis ◽

Life Years

8043 Background: IXA, CAR, ELO and DARin combination with LEN+DEXhave been found superior in efficacy compared to LEN+DEX in the management of R/R MM. Applying indirect treatment comparisons from a network meta-analysis (NMA), this economic evaluation aimed to estimate the comparative cost-effectiveness and cost-utility of these four triplet regimens in terms of progression-free survival (PFS). Methods: In the absence of direct treatment comparison from a single clinical trial, NMA was used to indirectly estimate the comparative PFS benefit of each regimen. A 2-state Markov model simulating the health outcomes and costs was used to evaluate PFS life years (LY) and quality-adjusted life years (QALY) with the triplet regimens over LEN+DEX and expressed as the incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR). Probability sensitivity analyses were conducted to assess the influence of parameter uncertainty on the model. Results: The NMA revealed that DAR+LEN+DEX was superior to the other triplet therapies, which did not differ statistically amongst them. As detailed in the Table, in our cost-effectiveness analysis, all 4 triplet regimens were associated with increased PFSLY and PFSQALY gained (g) over LEN+DEX at an additional cost. DAR+LEN+DEX emerged the most cost-effective with ICER and ICUR of $667,652/PFSLYg and $813,322/PFSQALYg, respectively. The highest probability of cost-effectiveness occurred at a willingness-to-pay threshold of $1,040,000/QALYg. Conclusions: Our economic analysis shows that all the triplet regimens were more expensive than LEN +DEX only but were also more effective with respect to PFSLY and PFSQALY gained. Relative to the other regimens, the daratumumab regimen was the most cost-effective.[Table: see text]

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Cost-utility Analysis of Second-generation Direct-acting Antivirals for Hepatitis C

Hepatitis Monthly ◽

10.5812/hepatmon118646 ◽

2021 ◽

Vol 21 (8) ◽

Author(s):

Abdollah Poursamad ◽

Zahra Goudarzi ◽

Iman Karimzadeh ◽

Nahid Jallaly ◽

Khosro Keshavarz ◽

...

Keyword(s):

Cost Effectiveness ◽

Hepatitis C ◽

Cost Effective ◽

Sensitivity Analyses ◽

Genotype 1 ◽

Medication Regimen ◽

Lifetime Horizon ◽

Medication Therapy ◽

Life Years ◽

Study Results

Background: Hepatitis C virus (HCV) can lead to increased mortality, disability, and liver transplantation if left untreated, and it is associated with a possible increase in disease burden in the future, all of which would surely have a significant impact on the health system. New antiviral regimens are effective in the treatment of the disease yet expensive. Objectives: The purpose of the present study was to assess the cost-effectiveness of three medication regimens, namely, ledipasvir/sofosbuvir (LDV/SOF), velpatasvir/sofosbuvir, and daclatasvir/sofosbuvir (DCV/SOF) for HCV patients with genotype 1 in Iran. Methods: A Markov model with a lifetime horizon was developed to predict the costs and outcomes of the three mentioned medication therapy strategies. The final outcome of the study was quality-adjusted life-years (QALYs), which was obtained using the previously published studies. The study was conducted from the perspective of the Health Ministry; therefore, only direct medical costs were estimated. The results were provided as the incremental cost-effectiveness ratio (ICER) per QALY. Ultimately, the one-way and probabilistic sensitivity analyses were used to measure the strength of study results. Results: The results showed that the QALYs for LDV/SOF, DCV/SOF, and VEL/SOF were 13.25, 13.94, and 14.61, and the costs were 4,807, 7,716, and 4,546$, respectively. The VEL/SOF regimen had lower costs and higher effectiveness than the LDV/SOF and DCV/SOF regimens, making it a dominant strategy. The tornado diagram results showed that the study results had the highest sensitivity to chronic hepatitis C (CHC) and compensated cirrhosis (CC) state costs. Moreover, the scatter plots showed that the VEL/SOF was the dominant therapeutic strategy in 73% of the simulations compared to LDV/SOF and 66% of the simulations compared to DCV/SOF; moreover, it was in the acceptable region in 92% of the simulations and below the threshold. Therefore, it was considered the most cost-effective strategy. Moreover, the results showed that DCV/SOF was in the acceptable region below the threshold in 69% of the simulations compared to LDV/SOF. Therefore, the DCV/SOF regimen was more cost-effective than LDV/SOF. Conclusions: According to the present study results, it is suggested that the VEL/SOF regimen be used as the first line of therapy in patients with HCV genotype 1. Moreover, DCV/SOF can be the second-line medication regimen.

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Cladribine tablets are a cost-effective strategy in high-disease activity relapsing multiple sclerosis patients in Iran

Current Journal of Neurology ◽

10.18502/cjn.v20i3.7690 ◽

2021 ◽

Author(s):

Nayyereh Ayati ◽

Lora Fleifel ◽

Mohammad Ali Sahraian ◽

Shekoufeh Nikfar

Keyword(s):

Multiple Sclerosis ◽

Cost Effectiveness ◽

Disease Activity ◽

Cost Effective ◽

High Disease Activity ◽

Sensitivity Analyses ◽

Life Years ◽

Multiple Sclerosis Patients ◽

The Cost ◽

Relapsing Multiple Sclerosis

Background: Cladribine tablets are the foremost oral immune-reconstitution therapy for high disease activity relapsing multiple sclerosis (HDA-RMS). We aimed to assess the cost-effectiveness of cladribine tablets compared to natalizumab in patients with HDA-RMS in Iran. Methods: A 5-year cohort-based Markov model was developed with 11 expanded disability status score (EDSS) health states, including patients with HDA-RMS as on and off-treatment. All costs were identified from the literature and expert opinion and were measured in Iranian Rial rates, changed to the 2020 USD rate and were discounted by 7.2%. Quality adjusted life years (QALY), discounted by 3.5%, and life years gained (LYG) were adopted to measure efficacy. The final results were presented as incremental cost-effectiveness ratio that was compared to a national willingness to pay (WTP) threshold of 1 to 3 gross domestic product (GDP) per capita. Deterministic and probabilistic sensitivity analyses (D/PSA) were employed to evaluate uncertainty. Results: Cladribine tablets dominated natalizumab and yielded 6,607 USD cost-saving and 0.003 additional QALYs per patient. LYG was comparable. The main cost component was drug acquisition cost in both arms. DSA indicated the sensitivity of the results to the cost discount rates and also the patients’ body weight; while they were less sensitive to the main clinical variables. PSA indicated that cladribine tablets were cost-effective in Iran, with a probability of 57.5% and 58.6% at lower and higher limits of threshold, respectively. Conclusion: Cladribine tablets yielded higher QALYs and lower costs compared to natalizumab, in patients with HDA-RMS in Iran.

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Fractionated Inotuzumab Ozogamicin Combined with Low-Intensity Chemotherapy Provides Very Good Outcome in Older Patients with Newly Diagnosed CD22+ Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia: First Results from the EWALL-INO Study

Blood ◽

10.1182/blood-2021-148625 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 511-511

Author(s):

Patrice Chevallier ◽

Thibault Leguay ◽

Michael Doubek ◽

Francoise Huguet ◽

Cyril Salek ◽

...

Keyword(s):

B Cell ◽

Older Patients ◽

Research Funding ◽

Lymphoblastic Leukemia ◽

Philadelphia Chromosome ◽

Newly Diagnosed ◽

Cell Precursor ◽

Inotuzumab Ozogamicin ◽

Low Intensity

Abstract On behalf of the GRAALL group, the Czech Republic ALL group, the Finland ALL group and the EWALL group. Introduction. Treatment of older patients (pts) with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains an unmet medical need. Inotuzumab ozogamicin (INO), an anti-CD22 antibody conjugated to calicheamicin, is approved for the treatment of relapsed/refractory BCP-ALL in adults, sinusoidal obstruction syndrome (SOS) being the major adverse event associated with INO. A previous first line study conducted by the MDACC in pts 60 years or older successfully used INO in combination with a lower intensity version of the hyper-CVAD (mini-hyper-CVD). Due to the occurrence of SOS, the total doses were fixed at 1.3 mg/m² for cycle 1 followed by 3 cycles at 1 mg/m² (Kantarjian H et al. Lancet Oncol, 2018). Here, we aimed to assess the activity and safety of fractionated INO at a reduced dosage in combination with low-intensity chemotherapy as frontline therapy for older pts with CD22+ Philadelphia chromosome-negative (Ph-neg) BCP-ALL. Methods. EWALL-INO is a single arm prospective phase 2 multicentric study conducted in European centers belonging to the EWALL group. Eligibility criteria were pts aged 55y or older, performance status ≤2, and newly diagnosed CD22+ (20% or more of positive blast cells) Ph-neg BCP-ALL without central nervous system involvement. After a prephase including 5 days (D) of dexamethasone (DEX) 10mg per D and a single intrathecal injection (IT), the induction regimen was begun and split in 2 parts. Induction part I (Induc1) consisted of one triple IT, vincristine (VCR) 2 mg (1 mg over 70y) D1 D8 D15 D22 and DEX 20 mg D1D2 D8D9 D15D16 D22D23 combined with 3 injections of INO (0.8 mg/m² D1, 0.5 mg/m² D8 and D15). Induction part II (Induc2) was offered to pts in CR or CRp (CR with platelets < 100 G/l) after Induc1 or as salvage therapy. Induc2 consisted of DEX 20mg D1D8, cyclophosphamide (CY) 300 mg/m² D1 to D3, one triple IT D2 and 2 injections of INO (0.5 mg/m² D1 and D8). Pts in CR/CRp were programmed to receive 6 blocks of consolidation (Ara-C 1.5g/m²/12h adapted to renal clearance D1D2 and DEX 10mg/12h D1D2, cycles 1 and 4; Methotrexate (MTX) 1.5 g/m² over 24h D1, VCR 1 or 2 mg D1, one triple IT D2 and 6-mercaptopurin (6-MP) D1 to D7, cycles 2 and 5; CY 500 mg/m² D1D2, VP16 75 mg/m² D1D2, one triple IT D2 and MTX 25 mg/m² D1, cycles 3 and 6) followed by a POMP maintenance (VCR, 6-MP, MTX, DEX) during 18 months. Allograft was allowed after at least 3 blocks of consolidation at the discretion of the investigators. The evaluable population was pts who received at least 1 dose of INO. Analyses were by modified intention to treat and performed JUN 28, 2021. All pts gave informed consent. The study is registered at ClinicalTrials.gov under the NCT number: NCT03249870. Results. Between DEC 29, 2017 and JUN 22, 2021, 115 pts (out of 130 planned pts) were enrolled including 6 pts with screen failure. The first 90 eligible pts (up to MAR 1, 2021) were considered for this analysis to obtain a minimum of 4 months follow-up. Median age was 69y (range 55-84) and median follow-up for alive pts was 1.18 years (range 0.3-3.5). At time of analysis, 90 and 88 pts had started induc1 and induc2, respectively. Treatment related mortality was 2.2% (2/90) and CR/CRp rate was 85.5% (77/90, 6 CRp) after induc1. Three cases relapsed between induc1 and induc2 and 5 pts were salvaged by induc2 allowing to a CR/CRp rate of 87.7% (79/90, 8 CRp) after induc2. One pts died from refractory disease during induc2. One, 2, 3 4 and 5 injections of INO were administered to 2 (2.2%), 2(2.2%), 11 (12.2%), 2 (2.2%) and 73 pts (81.1%) respectively. Only 6 pts were allografted. One-year OS was estimated to be 78.5% (95%CI 68-85.9) and median OS was not reached. One-year relapse free survival was 74.5% (95CI 63.5-82.6) (Figure 1). Grade 3-4 liver toxicity was observed in 8 pts (8.8%) during the study including 3 pts (3.3%) developing SOS, 2 related to INO during induc1 and one occurred after transplant. Twenty-nine pts died during the follow-up, 16 from relapses (overall incidence 18%) and 13 from adverse events (overall incidence 14.4%), including one COVID19 fatal infection during consolidation. Conclusion. Fractionated inotuzumab ozogamicin at reduced doses (0.8/0.5/0.5/0.5 mg/m²) combined with low-intensity chemotherapy is a very active and well tolerated frontline therapy for older patients with CD22+ Ph-neg BCP-ALL. Figure 1 Figure 1. Disclosures Doubek: Janssen-Cilag, AbbVie, AstraZeneca, Amgen, Gilead, Novartis: Honoraria, Research Funding. Huguet: Novartis: Other: Advisor; Jazz Pharmaceuticals: Other: Advisor; Celgene: Other: Advisor; BMS: Other: Advisor; Amgen: Other: Advisor; Pfizer: Other: Advisor. Raffoux: ABBVIE: Consultancy; PFIZER: Consultancy; CELGENE/BMS: Consultancy; ASTELLAS: Consultancy. Boissel: CELGENE: Honoraria; Servier: Consultancy, Honoraria; Incyte: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; PFIZER: Consultancy, Honoraria; JAZZ Pharma: Honoraria, Research Funding; SANOFI: Honoraria. Dombret: Amgen: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Novartis: Research Funding; Pfizer: Honoraria, Research Funding; Servier: Research Funding; Abbvie: Honoraria; BMS-Celgene: Honoraria; Daiichi Sankyo: Honoraria. Rousselot: Incyte, Pfizer: Consultancy, Research Funding. OffLabel Disclosure: Inotuzumab ozogamicin as first line therapy in newly diagnosed CD22+ Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia

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