Zanubrutinib vs. Acalabrutinib in B-Cell Malignancies: An Adverse Event-Based Economic Analysis
Talha Munir*1, Vincent Levy2, Leyla Mohseninejad3, Tushar Srivastava4, Anurag Gupta5, Raju Gautam4,Keri Yang6, Rhys Williams6, Shouhao Zhou7, Yucai Wang8
1Leeds Teaching Hospital NHS Trust, Leeds, West Yorkshire, United Kingdom, 2Hôpital Avicenne, AP-HP etUniversité Sorbonne, Paris Nord, France, 3BeiGene Netherlands B.V., Schiphol, The Netherlands,4ConnectHEOR, London, United Kingdom, 5ConnectHEOR, Delhi, India, 6BeiGene USA, Inc., San Mateo, CA,United States of America, 7Division of Biostatistics and Bioinformatics, Penn State College of Medicine,Hershey, PA, United States of America, 8Division of Hematology, Mayo Clinic, Rochester, MN, UnitedStates of America

Background: B-cell malignancies comprise a heterogenous group of cancers, including B-cell lymphoma,
B-cell leukemias, and plasma cell dyscrasias. In clinical trials for B-cell malignancies, the 2nd generation
Bruton tyrosine kinase inhibitors (BTKis) zanubrutinib and acalabrutinib had improved safety vs the 1stgeneration BTKi ibrutinib; however, direct comparison of 2nd generation BTKi is lacking. A recent metaanalysis provided a comprehensive, indirect comparison of the adverse event (AE) profiles ofacalabrutinib and zanubrutinib in clinical trials for B-cell malignancies (Hwang et al. Hemasphere.
2023;7(S3):1134).
Aims: This study aims to evaluate impacts on costs and quality of life (QoL) for zanubrutinib vsacalabrutinib from the United Kingdom (UK) healthcare perspective using the AE profiles from Hwang etal.
Methods: The cost and QoL associated with AE management for zanubrutinib and acalabrutinib weredetermined using a health economic model developed from the UK’s National Health Service (NHS)
perspective. Model inputs included: incidence rates (IRs) of all grade and grade ≥3 AEs of interest (n=21;e.g., bleeding events, hypertension, atrial fibrillation, cytopenias, infections, headache, arthralgia,diarrhea), as reported in the meta-analysis; disutility and mean duration of AEs, as reported in publishedarticles and previous single technology appraisals performed by the National Institute of Health andCare Excellence (NICE); and the unit cost of each AE, based on the National Schedule of NHS costs
database (FY 2021-22), AE specific Healthcare Resource Group (HRG) codes, and consultation withclinical experts. Unit costs were inflated to 2023 GBP (£). Model outcomes were AE management cost(=𝐼𝐼𝐼𝐼 ∗ 𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐) and quality-adjusted life years (QALYs) lost due to AEs (=𝐼𝐼𝐼𝐼 ∗ 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 ∗𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷/365.25). Robustness of the analysis was tested using probabilistic sensitivity analysis (PSA).
Results: In the base case (considering all AEs), treatment of a hypothetical cohort of 1000 patients withzanubrutinib instead of acalabrutinib was associated with cost savings of £413K and 3.69 QALY gains(i.e., 3.69 years extra in full health) (Figure 1). Subgroup analysis for grade ≥3 AEs (£148K cost savings,
1.80 QALY gains) and grade 1-2 AEs (£264K cost savings, 1.89 QALY gains) showed similar trends. Asensitivity analysis limited to AEs significantly different between zanubrutinib and acalabrutinib (n=13)
yielded consistent results (£442K cost savings, 3.88 QALY gains). A PSA, conducted with 1000 iterations
to account for uncertainty in model parameters, confirmed robustness, indicating stable conclusions
across a wide range of parameter uncertainties.
EHA 2024

Summary/Conclusion: The results of this economic analysis indicate that zanubrutinib was cost-saving
and associated with added health benefits compared to acalabrutinib in terms of AE management inpatients with B-cell malignancies in the UK. If these results derived from meta-analysis of clinical trial
data could be assumed generalizable to the real-world patients across different indications, the savings
could be substantial.

EHA 2024