Zanubrutinib Associated With Cost Savings and QALY Benefits vs Acalabrutinib in B-Cell Malignancies

Talha Munir, MBChB, PhD

Data from an adverse effect (AE)–based economic analysis in the United Kingdom found that treatment with zanubrutinib (Brukinsa) was associated with cost savings and quality-adjusted life year (QALY) benefits vs treatment with acalabrutinib (Calquence) in patients with B-cell malignancies.¹

Findings presented at the 2024 EHA Congress showed when considering all AEs, treatment of a hypothetical cohort of 1000 patients using zanubrutinib instead of acalabrutinib translated to a cost savings of £599,000 and a QALY savings of 3.7. The cost of managing AEs for zanubrutinib was £2,331,858 compared with £2,930,429 for acalabrutinib. The QALYs lost due to AEs were 9.4 and 13.1, respectively.

The next-generation BTK inhibitors have displayed efficacy in clinical trials for patients with B-cell malignancies with improved safety profiles compared with the first-generation BTK inhibitor ibrutinib (Imbruvica). Although head-to-head data for zanubrutinib vs acalabrutinib are lacking, findings from a meta-analysis presented at the 2023 EHA Congress by Steven Hwang, MD, of Mayo Clinic in Rochester, Minnesota, and colleagues, showed that both acalabrutinib and zanubrutinib were associated with improved AE profiles compared with ibrutinib.²

In the meta-analysis, higher rates of infections, atrial fibrillation, diarrhea, nausea/vomiting, headaches, cough, fatigue, and pyrexia were observed for acalabrutinib vs zanubrutinib. Zanubrutinib was tied to higher rates of hematuria, neutropenia, and hypertension compared with acalabrutinib.

“If we conclude that the results from the meta-analysis of clinical trial data are assumed to be generalizable to the real-world population, the benefits [of zanubrutinib vs acalabrutinib] to the patients and payers would be substantial," lead study author of the AE-based economic analysis, Talha Munir, MBChB, PhD, of Leeds Teaching Hospital NHS Trust in West Yorkshire, United Kingdom, said during a presentation of the data.¹

Based on the AE profiles reported for zanubrutinib and acalabrutinib in the meta-analysis, Munir and colleagues sought to further analyze the cost and quality-of-life (QOL) outcomes for the 2 agents.

In the economic analysis, investigators calculated the total costs of managing AEs by adding the estimated costs of managing grade 3 or higher AEs and grade 1/2 toxicities. QALY loss was determined by multiplying the incidence rates with disutility weights assigned to them and their duration.

The incidence rates for any-grade and grade 3 or higher AEs included 20 different toxicities sourced from Hwang’s meta-analysis. Notably, cellulitis data were excluded from the economic analysis due to a data error reported by Hwang and colleagues. Disutility and average duration of AEs were sourced from published literature and prior single technology appraisals (STAs) from The National Institute for Health and Care Excellence (NICE) in the United Kingdom. Although the disutility and duration data for grade 3 or higher AEs were pulled from literature and NICE STAs, disutility of grade 1/2 AEs were assumed to be less than 30% of corresponding severe AEs due to a lack of evidence reporting the disutility of low-grade AEs. These assumptions were validated by clinical experts.

The unit cost of each AE was pulled from the National Schedule of NHS costs database in consultation with clinical experts, with costs inflated to match the 2023 Great Britain pound sterling. For AE data that could not be obtained via literature, investigators used a substitute value for a closely related toxicity, chosen in consultation with clinical experts.

Munir and colleagues conducted 3 types of analyses:

• Base case: all AEs for a hypothetical cohort of 1000 patients treated in clinical practice with zanubrutinib and acalabrutinib
• Scenario: Grade 3 or higher AEs, grade 1/2 AEs, and AEs with a statistically significant difference between zanubrutinib and acalabrutinib
• Sensitivity: Uncertainty around model parameters estimated in a one-way sensitivity analysis (OWSA); and consistency of results checked by probabilistic sensitivity analysis (PSA) with 1000 iterations, assuming the appropriate statistical distributions for parameters

Additional data from the scenario analysis showed similar trends regarding cost savings and QALY savings for zanubrutinib vs acalabrutinib. Notably, this analysis was limited to AEs with statistically significant differences between the 2 agents.

For specific-grade AEs in the hypothetical cohort, the cost savings for zanubrutinib vs acalabrutinib were £215,331 for grade 3 or higher AEs and £383,240 for grade 1/2 AEs. The respective QALY savings were 1.8 and 1.9. For significantly different AEs in the hypothetical cohort, the costs savings for zanubrutinib vs acalabrutinib were £627,638 for all-grade AEs, £219,749 for grade 3 or higher AEs, and £407,889 for grade 1/2 AEs. The respective QALY savings were 3.9, 1.8, and 2.1.

In both the base case and scenario analyses, cost savings were impacted more by grade 1/2 AEs (base case, 64%; scenario, 65%) compared with grade 3 or higher AEs (36%; 35%). In these analyses, QALY savings were similar between grade 1/2 AEs (base case, 51%; scenario, 54%) and grade 3 or higher AEs (49%; 46%).

Findings from the OWSA showed that the incidence rate of infections was the most influential factor affecting cost savings, and disutility associated with the incidence rates of headache and infection for acalabrutinib contributed the most to parameters influencing QALY. The PSA data were consistent with the base case analysis.

Munir concluded by noting that the economic analysis was limited by the lack of direct data available for the disutility and duration of particular AEs, which investigators attempted to mitigate with the input of clinical experts. Additionally, the economic and QOL benefits derived from this analysis were limited to AEs, and efficacy for both agents was not considered.

“The strength of the study is that there was a robust analysis…to evaluate the safety profile of zanubrutinib compared with acalabrutinib, and this [economic analysis] is on the ground of the independent meta-analysis performed by Hwang et al. There is some solid foundation of existing scientific evidence,” Munir concluded.

Disclosures: Dr Munir reported receiving honoraria from Janssen, AbbVie, Gilead, Alexion, Novartis, and Roche; and consulting with MorphoSys and Sunesis. This study was sponsored by BeiGene.

References

1. Munir T, Levy V, Mohseninejad L, et al. Zanubrutinib versus acalabrutinib in B-cell malignancies: an adverse event-based economic analysis. Presented at: 2024 EHA Congress; June 13-16, 2024; Madrid, Spain. Abstract S333.
2. Hwang S, Wang J, Tian Z, et al. Comparison of treatment-emergent adverse events of acalabrutinib and zanubrutinib in clinical trials in B-cell malignancies: a systemic review and meta-analysis. Presented at: 2023 EHA Congress; June 8-11, 2023; Frankfurt, Germany. Abstract P632.