Zanubrutinib is a second-generation Bruton tyrosine kinase (BTK) inhibitor that has fewer off-target effects and less cardiotoxicity than ibrutinib, a first-generation BTK inhibitor.
Changes to the National Comprehensive Cancer Network (NCCN) guidelines in chronic lymphocytic leukemia and small lymphocytic leukemia (CLL/SLL) give preference to the Bruton tyrosine kinase (BTK) inhibitor zanubrutinib for several groups of patients, including some receiving first-line therapy. The updates were published on January 18, 2022.1
Zanubrutinib, sold as Brukinsa by BeiGene, is a second-generation BTK inhibitor that has fewer off-target effects and less cardiotoxicity than ibrutinib, a first-generation BTK inhibitor.2
According to the updated guidelines, zanubrutinib is now a preferred therapy for first-line treatment of patients with CLL/SLL who do not have the deletion(17p) / TP53 mutation; the recommendation was given a grade of 2A, which means it is based on lower-level evidence but there is uniform consensus that the recommendation is appropriate.
For patients with CLL/SLL without deletion(17p) / TP53 mutation who are receiving second-line or subsequent therapy, zanubrutinib was moved from “other recommended regimen” to “preferred regimen.” The statement that recommended zanubrutinib to patients with a contraindication to other BTK inhibitors was removed.
For both updates, the recommendations extended to patients older or younger than 65 years, with or without comorbidities.
For those patients who have CLL/SLL with the deletion(17p) / TP53 mutation zanubrutinib is now a preferred therapy in both first- and second-line treatment, according to the updated guidelines. Again, zanubrutinib was moved from “other recommended regimen” to “preferred regimen,” and the qualifying statement that the drug be given to patients with a contraindication to other BTK inhibitors was removed.
In addition, under special considerations for the use of small-molecule inhibitors, there is updated information on adverse events of special interest, based on evidence published in 2020 by Constantine Tam, MBBS, MD, a hematologist and CLL expert at the Peter MacCallum Cancer Centre in Victoria, Australia.3
In December 2021, at the American Society of Hematology Meeting & Exposition in Atlanta, Tam presented results of the SEQUOIA trial,4 which found that zanubrutinib improved progression-free survival by 58% compared with bendamustine plus rituximab in patients with treatment-naïve CLL/SLL; Tam presented results from the cohorts of patients in SEQUOIA who did not have deletion(17p).
1. NCCN. Clinical Practice Guidelines in Oncology. Chronic lymphocytic leukemia/small lymphocytic leukemia, version 2.2022. Accessed January 19, 2022. https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf
2. Shaw ML. Second-generation BTK inhibitors hit the treatment bullseye with fewer off-treatment target effects. Am J Manag Care. 2020;26(7 Spec No):SP226-SP227. doi:10.37765/ajmc.2020.88475
3. Tam CS, Robak T, Ghia P, et al. Zanubrutinib monotherapy for patients with treatment naïve chronic lymphocytic leukemia and 17p deletion. Haematologica. 2020;106(9):2354-2363. doi:10.3324/haematol.2020.259432
4. Tam CS, Giannopoulous K, Jurczak W, et al. SEQUOIA: results of a phase 3 randomized study of zanubrutinib versus bendamustine + rituximab (BR) in patients with treatment-naïve (TN) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Presented at: 63rd Annual American Society of Hematology Meeting & Exposition; Atlanta, GA; December 12, 2021; Abstract 396. https://ash.confex.com/ash/2021/webprogram/Paper148457.html