The National Comprehensive Cancer Network recommendations come as the FDA weighs an indication in chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) for zanubrutinib.
As drugmaker BeiGene awaits word from the FDA on whether zanubrutinib will receive an additional indication in chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL), a key stakeholder has already weighed in.
The National Comprehensive Cancer Network (NCCN) guidelines committee, which had previously included zanubrutinib in its recommendations, has placed the second-generation Bruton tyrosine kinase (BTK) inhibitor on a higher rung in the guidelines in several areas.
Meanwhile, ibrutinib, a first-generation BTK inhibitor, has lost priority due to its toxicity profile.1
In June, BeiGene announced that FDA would postpone the target action date for a CLL/SLL indication for zanubrutinib until January 20, 2023.2
BeiGene had asked the agency to include new data from the ALPINE trial (NCT03734016) that showed a superior overall response rate compared with ibrutinib.3 This was deemed a major amendment by FDA; since that time, presentations at the European Hematology Association on data from ALPINE and the SEQUOIA trial (NCT03336333) also showed superior quality of life for zanubrutinib.4
Besides listing preferred and other recommended regimens, the NCCN committees put regimens in categories based on levels of evidence. A category 1 recommendation is based on “uniform NCCN consensus” based on “high-level evidence,” whereas a category 2A recommendation is based on “lower-level evidence” with “uniform consensus,” and 2B indicates “lower-level evidence” with “NCCN consensus.”
Among the key changes in its update, released August 30, 2022, the NCCN panel on CLL/SLL guidelines put notations on ibrutinib’s recommendation based on its toxicity profile. The first-generation BTK inhibitor is known to have “off target” cardiac effects.
Changes in CLL/SLL without del(17p)/TP53 mutation for first-line therapy include the following:
For CLL/SLL without del(17p)/TP53 mutation in second-line and subsequent therapy:
Under recommendations for CLL/SLL with del(17p)/TP53 mutation:
Zanubrutinib, sold as Brukinsa, is approved by FDA for adult patients with Waldenström macroglobulinemia, those with mantle cell lymphoma who have received at least 1 prior therapy, and those with relapsed/refractory marginal zone lymphoma who have received at least 1 anti-CD20–based regimen.
1. NCCN. Clinical Practice Guidelines in Oncology. Chronic lymphocytic leukemia/small lymphocytic leukemia, version 1.2023. Accessed September 7, 2022. https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf
2. BeiGene announces PDUFA goal date extension for US sNDA for Brukinsa for the treatment of CLL/SLL. News release. BeiGene. June 13, 2022. Accessed September 7, 2022. https://bwnews.pr/3xixTm3
3. Rosa K. Final response analysis of ALPINE trial shows superior ORR with zanubrutinib vs ibrutinib in CLL. OncLive®. April 11, 2022. Accessed September 7, 2022. https://www.onclive.com/view/final-response-analysis-of-alpine-trial-shows-superior-orr-with-zanubrutinib-vs-ibrutinib-in-cll
4. Mattina C. ALPINE, SEQUOIA findings: zanubrutinib offers improved HRQOL in CLL/SLL. The American Journal of Managed Care® website. June 11, 2022. Accessed September 7, 2022. https://www.ajmc.com/view/alpine-sequoia-findings-zanubrutinib-offers-improved-hrqol-in-cll-sll