Zanubrutinib Offers Clinical and Cost Benefits Over Acalabrutinib in R/R CLL

A new health-economic model suggests that zanubrutinib (Brukinsa) provides superior clinical and economic outcomes compared with acalabrutinib (Calquence) for patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL), including those with high-risk features.¹

The study, published in Future Oncology, utilized a number needed to treat (NNT) framework to quantify the clinical benefit, determining that 10 patients with CLL would need to be treated with zanubrutinib instead of acalabrutinib to avoid 1 additional case of disease progression and 15 patients to avoid 1 additional death, yielding a per-patient cost-savings of $7,335 over 24 months.

Furthermore, among those with high-risk disease, the clinical and economic benefits over acalabrutinib are more pronounced, with an NNT of 6 needed to prevent 1 disease progression and an NNT of 18 needed to avoid 1 death, yielding an even greater total cost-savings of $11,533.

“The NNT analysis suggests potential clinical benefits and potential savings for health systems from treating patients with R/R CLL and high-risk R/R CLL with zanubrutinib,” wrote authors Shadman et al in the publication.¹

As the landscape for R/R CLL shifts toward second-generation Bruton tyrosine kinase (BTK) inhibitors, clinicians and payers face the challenge of differentiating between agents in the absence of a direct head-to-head clinical trial. This study sought to bridge this gap by comparing data from the phase 3 ALPINE trial (NCT03734016),² which evaluated zanubrutinib, and the phase 3 ASCEND trial (NCT02970318),³ which evaluated acalabrutinib.

Notably, this analysis is distinct from a previous analysis that compared BTK inhibitors across multiple phase 3 trials—ALPINE, ASCEND, AND ELEVATE-RR (NCT02477696)—also published earlier this year by Shadman and colleagues in the Journal of Medical Economics. Here, zanubrutinib was associated with significantly prolonged progression-free survival (PFS) vs acalabrutinib and ibrutinib (Imbruvica) in the R/R CLL patient population.⁴

While the previous study focused on estimating relative comparative clinical efficacy, the present study translates those differences into more practical terms. Specifically, it estimates how many patients would need to be treated with a particular BTK inhibitor instead of another to prevent an additional progression or death and also examines the associated cost implications over 24 months.

Clinical Efficacy Findings

The researchers employed a matching-adjusted indirect comparison framework to account for differences in patient populations across the 2 trials, adjusting for factors such as age, ECOG performance status, and genomic mutations.

After adjustment, zanubrutinib demonstrated a higher PFS rate across all evaluated time points. At 12 months, the estimated PFS was 93.2% for zanubrutinib vs 88.1% for acalabrutinib. By 24 months, the gap persisted, with PFS rates of 85.5% and 75.1%, respectively.

Economic Implications for Oncology Practices

Beyond clinical efficacy, the study conducted a cost-effectiveness analysis from a US payer perspective. The monthly wholesale acquisition cost for zanubrutinib was slightly lower than that for acalabrutinib ($15,744 vs $15,829). Importantly, the study found that zanubrutinib was associated with a lower cost per patient-month in remission.

The findings indicate that the clinical superiority of zanubrutinib in terms of PFS results in a more favorable value proposition. For clinicians managing high-volume practices, these metrics provide a standardized way to evaluate the long-term economic impact of treatment selection in the second-line or greater setting.

REFERENCES

1. Shadman M, Chanan-Khan A, Campbell D, et al. Number needed to treat to avoid progression and death and cost analysis: zanubrutinib versus acalabrutinib in relapsed/refractory chronic lymphocytic leukemia. Future Oncol. 2026;22(3):339-348. doi:10.1080/14796694.2026.2615736

2. A study of zanubrutinib (BGB-3111) versus ibrutinib in participants with relapsed/refractory chronic lymphocytic leukemia (ALPINE). ClinicalTrials.gov. Updated March 30, 2025. Accessed March 4, 2026. https://clinicaltrials.gov/study/NCT03734016

3. A study of acalabrutinib vs investigator's choice of idelalisib plus rituximab or bendamustine plus rituximab in R/R CLL. ClinicalTrials.gov. Updated February 6, 2026. Accessed March 4, 2026. https://clinicaltrials.gov/study/NCT02970318

4. Shadman M, Bouwmeester W, Mohseninejad L, et al. Prolonged progression-free survival with zanubrutinib in relapsed/refractory CLL: an indirect treatment comparison versus other BTK inhibitors using multilevel network meta-regression. J Med Econ. 2026;29(1):180-192. doi:10.1080/13696998.2025.2609514