Zanubrutinib receives FDA approval for the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma
Zanubrutinib was approved by the Food and Drug Administration (FDA) on the 19th of January 2023, for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL)1.
Zanubrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor, which prevents activation of the B-cell antigen receptor (BCR) signaling pathway, causing suppression of malignant B-cell growth2. It was previously approved for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL) in 20193. Its approval for CLL and SLL is based on two recent Phase III clinical trials, SEQUOIA (NCT03336333)4 and ALPINE (NCT03734016)5. The SEQUOIA trial assessed zanubrutinib versus bendamustine and rituximab (BR) in treatment-naïve patients with CLL and SLL, and reported a superior event-free survival (EFS) at 24 months of 85.5% (95% CI 80, 90) with zanubrutinib compared to 69.5% (95% CI: 62, 80) with BR4. Additionally, the Phase III ALPINE study assessed zanubrutinib versus ibrutinib in patients with R/R CLL/SLL who had undergone 1-8 prior lines of therapy, and also reported a superior PFS at 24 months in the zanubrutinib group of 78.4% (95% CI: 73, 83) compared with 65.9% (95% CI: 60, 71) with ibrutinib, and an overall response rate (ORR) of 80% (95% CI: 76, 85) with zanubrutinib compared to 73% (95% CI: 68, 78) with ibrutinib5.
The most common adverse events reported across both studies were neutropenia, upper respiratory tract infection, thrombocytopenia, hemorrhage, and musculoskeletal pain1. However, zanubrutinib exhibited a more manageable toxicity profile relative to other treatments in both trials4,5.
In an exclusive interview at the 2022 American Society of Hematology (ASH) congress, Mazyar Shadman, MD, Fred Hutchinson Cancer Research Center, Seattle, WA, discussed promising results from the ALPINE study stating that, “with the data showing an improved progression-free survival, shown for the first time in CLL, [zanubrutinib] can potentially change the treatment landscape for CLL patients.”
The approval of zanubrutinib is a step forward for both treatment-naïve and R/R patients with CLL and SLL.
1. US Food and Drug Administration. FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma. Available from: Here. (Last accessed 23/01/2023).
2. National Center for Biotechnology Information. PubChem Compound Summary for CID 135565884, Zanubrutinib. Available from: Here. (Last accessed 23/01/2023).
3. US Food and Drug Administration. FDA approves therapy to treat patients with relapsed and refractory mantle cell lymphoma supported by clinical trial results showing high response rate of tumor shrinkage. Available from: Here. (Last accessed 23/01/2023).
4. Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncology. 2022 July 7;23(8):1031-43.
5. Brown JR, Eichhorst B, Hillmen P, et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. New England Journal of Medicine. 2022 December 13.
Written by Amy Preston
Edited by Elitsa Kamberska and Thomas Southgate