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
Authors: Delea Thomas , Despiegel Nicholas , Boyko Diana , Amdahl Jordan , Cong Ze , Radich Jerald 
Published: October 2019

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.