ASH 2021: Early Results With Zanubrutinib Plus Venetoclax in High-Risk CLL
Posted: Wednesday, December 15, 2021
The combination of the Bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib and venetoclax appears to be well tolerated in patients with treatment-naive chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) with deletion of chromosome 17p13 [del(17p)]. These early results are from arm D of the phase III SEQUOIA trial, presented at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 67). According to Alessandra Tedeschi, MD, of Niguarda Hospital, Milan, Italy, and colleagues, no new safety signals were reported in this high-risk population.
In this open-label, multicenter trial, 35 patients with centrally confirmed del(17p) were enrolled to receive zanubrutinib at 160 mg twice daily for 3 months followed by zanubrutinib at 160 mg plus venetoclax at 400 mg following a ramp-up cycle. Almost all patients (94.3%) had CLL and high-risk characteristics including Binet stage C (51.5%), bulky disease (42.9%), unmutated IGHV locus (85.3%), elevated β2-microglobulin (71.4%), and a median del(17p) frequency of 81.5%.
As for safety, adverse events and serious adverse events were reported in 29 patients (82.9%) and 4 patients (11.4%), respectively. The most common adverse events included diarrhea (n = 5), neutropenia (n = 5), fatigue (n = 4), nausea (n = 4), and petechiae (n = 4). One-third of patients experienced grade 3 or higher adverse events. To date, no tumor-lysis syndrome has been reported.
Among the 31 patients who reached the initial efficacy assessment at 3 months after starting zanubrutinib, the overall response rate was 96.8%. Progressive disease was reported in one patient after having an initial partial response while on combination therapy. Enrollment in the study continues, with a goal of approximately 80 patients.
Disclosures: For full disclosures of the study authors, visit ash.confex.com.