Efficacy and Cost Savings of Zanubrutinib in High-Risk R/R CLL

Treating patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) with zanubrutinib (Brukinsa; BeOne) vs acalabrutinib (Calquence; AstraZeneca) leads to a lower risk of progression and death, as well as significant per-patient cost savings, according to a new report published in Future Oncology. The findings are based on a number-needed-to-treat analysis.¹

In comparing the 2 drugs, the study essentially aimed to measure the improvement of different Bruton tyrosine kinase inhibitors (BTKi) over time. The first-generation BTKi, ibrutinib (Imbruvica), led to a marked improvement in CLL outcomes, but it also came with a significant risk of cardiac adverse events, including atrial fibrillation.²

Acalabrutinib is a second-generation BTKi. It conveyed the same benefits of BTKis in patients with R/R CLL, but with a lower cardiotoxicity risk.³

Zanubrutinib, meanwhile, is a next-generation BTKi that “was designed for greater BTK specificity, sustained occupancy, and increased potency compared with ibrutinib and acalabrutinib,” the authors of the study, which was funded by BeOne Medicines, explained.¹

Yet, there is little in the way of head-to-head comparative data examining the efficacy of zanubrutinib versus acalabrutinib in patients with R/R CLL, the authors explained. They decided to help fill that gap by looking at the outcomes of the 2 therapies with regard to both efficacy and medical costs. They chose to look at both the R/R CLL population in general and at the high-risk population specifically. Patients were classified as high-risk if they had a detectable deletion of chromosomes 17p or 11q, mutations in the TP53 gene, or an unmutated immunoglobulin heavy-chain variable region gene.

To perform their economic analysis, the investigators built upon an earlier matching-adjusted indirect comparison of the 2 therapies that used data from the ALPINE and ASCEND trials of zanubrutinib and acalabrutinib, respectively.⁴

Their goal was to see how many people needed to be treated to avoid one disease progression or death, as well as the economic impacts of such treatment. They developed a base case that showed using zanubrutinib instead of acalabrutinib avoided one R/R CLL progression for every 10 patients (for a number needed to treat [NNT] of 10). The NNT to avoid one death was 15, they found.

“Using real-world treatment utilization data from the Symphony database, the model estimated 94 real-world deaths could have been avoided over a 2-year period if patients receiving acalabrutinib had instead been treated with zanubrutinib,” the authors said. The Symphony Integrated Dataverse database is a large medical claims database that is estimated to include healthcare claims for 30% to 50% of patients with CLL in the US, the authors said.

Among high-risk patients, the NNT to avoid one progression was 6, and the NNT to avoid one death was 18, they found.

In terms of healthcare spending, the investigators found that the per-patient cost savings associated with using zanubrutinib instead of acalabrutinib were $7335 over the course of 24 months in the general R/R CLL group and $11,533 among high-risk patients.

“The cost savings were driven by lower subsequent treatment and disease management costs associated with disease progression,” the authors said. “The model results were robust with persistent savings over sensitivity analyses.”

The investigators said they used real-world studies to derive the costs built into their models, though they said those data are general and may not reflect specific treatments or specific populations. They also noted that their study did not include other important factors affecting treatment decisions, such as patient quality of life.

Overall, though, the investigators said their data show the next-generation BTKi zanubrutinib provides a meaningful benefit, both on the patient level and on a macroeconomic level.

“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,” they concluded.

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. Paydas S. Management of adverse effects/toxicity of ibrutinib. Crit Rev Oncol Hematol. 2019;136:56-63. doi:10.1016/j.critrevonc.2019.02.001
3. Seymour JF, Byrd JC, Ghia P, et al. Detailed safety profile of acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia in the ELEVATE-RR trial. Blood. 2023;142(8):687-699. doi:10.1182/blood.2022018818
4. Shadman M, Brown JR, Williams R, et al. Efficacy of zanubrutinib versus acalabrutinib for relapsed or refractory chronic lymphocytic leukemia (R/R CLL): a matching-adjusted indirect comparison (MAIC). Ther Adv Med Oncol. 2025;17:17588359251340554. doi:10.1177/17588359251340554