Zanubrutinib, Venetoclax Combination Therapy Well-Tolerated in Certain Patients With CLL or SLL

The combination therapy of zanubrutinib (Brukinsa, BeiGene) and venetoclax was well-tolerated in treatment-naïve (TN) patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) and the high-risk feature, deletion of chromosome 17p13.1 (del(17p)), according to the early results from arm D of the SEQUOIA trial presented at the 2021 American Society of Hematology Annual Meeting and Exposition. The investigators said that there were no new safety signals identified, and no reported instances of tumor lysis syndrome (TLS).¹

SEQUOIA is an open-label, global, multicenter, phase 3 study which contains a non-randomized cohort (Arm D) of patients with TN del(17p) CLL/SLL. These patients were treated with zanubrutinib at a dosage of 160 mg twice daily for 3 months before venetoclax was introduced via a ramp-up cycle followed by 400 mg once daily. The combination treatment was then delivered for 12 to 24 cycles until disease progression, unacceptable toxicity, or achievement of uMRD at <10-4 sensitivity by flow cytometry.¹

At the time of the data cutoff, 35 of approximately 80 planned patients with centrally confirmed del(17p) were enrolled. The median follow-up was 9.7 months. According to the study results, 94.3% of the safety analysis population had CLL and high-risk characteristics, including Binet stage C (51.5%), bulky disease ≥5 cm (42.9%), unmutated immunoglobulin heavy chain variable locus (85.3%, n=34), median del(17p) frequency of 81.5%, and elevated β2-microglobulin (71.4%).¹

The investigators reported that adverse events (AEs) occurred in 82.9% of the study population, with serious AEs observed in 11.4% of patients. AEs reported in ≥10% of patients included diarrhea (n=5), neutropenia (n=5), fatigue (n=4), nausea (n=4), and petechiae (n=4). Thirteen patients had grade ≥3 AEs, most frequently neutropenia (n=4) and diarrhea (n=2).¹

“Together with ALPINE, the positive SEQUOIA trial provides evidence that Brukinsa can improve treatment outcomes for patients with CLL,” said Jane Huang, MD, chief medical officer of hematology at BeiGene, in a press release. “Data at ASH this year reinforce our belief that Brukinsa’s differentiated design can bring patients clinical benefits, including those who experience treatment discontinuation with other BTK inhibitors. We look forward to sharing more details on our clinical progress in our hematology portfolio with the medical community in Atlanta.”²

In a press release from BeiGene, the company announced that this combination therapy had been associated with improved outcomes for patients with CLL. Improvements in progression-free survival compared to bendamustine and rituximab were statistically significant, and efficacy results were consistent between the assessments of the independent review committee and the investigators.²

REFERENCES

1. Tedeschi A, Ferrant E, Flinn IW, et al. Zanubrutinib in combination with venetoclax for patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with del(17p): early results from arm d of the SEQUOIA (BGB-3111-304) trial. Presented at: ASH Annual Meeting and Exposition 2021. Accessed December 7, 2021. https://ash.confex.com/ash/2021/webprogram/Paper144336.html
2. BeiGene to present clinical data on Brukinsa in chronic lymphocytic leukemia at the 63rd ASH annual meeting [news release]. BeiGene; November 4, 2021. Accessed December 7, 2021. https://www.businesswire.com/news/home/20211104005231/en/