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SEQUOIA: Zanubrutinib meets primary endpoint for treatment-naïve CLL/SLL

Presented by
Prof. Constantine Tam, Peter MacCallum Cancer Centre, Australia
ASH 2021
Phase 3, SEQUOIA
Zanubrutinib outperformed bendamustine plus rituximab in patients with treatment-naïve chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL). The effect was consistent across high-risk subgroups, such as patients with unmutated IGHV or del(11q). The results of this phase 3 trial showed that zanubrutinib, a chemotherapy-free therapy, is an effective frontline therapy for patients with CLL/SLL [1].

Zanubrutinub is a second-generation Bruton’s tyrosine kinase (BTK) inhibitor that has demonstrated favourable efficacy and safety in patients with Waldenström macroglobulinaemia and relapsed refractory CLL/SLL [2,3]. Cohort 1 of the current open-label, phase 3 SEQUOIA trial (NCT03336333) randomised 479 patients with treatment-naïve CLL/SLL without del(17p) who were unfit for intensive chemotherapy 1:1 to zanubrutinib (160 mg, twice daily) or a regimen of bendamustine plus rituximab. The primary endpoint was progression-free survival (PFS) at 24 months. Prof. Constantine Tam (Peter MacCallum Cancer Centre, Australia) presented the primary results.

At 24 months, PFS rates favoured zanubrutinib (85.5%) over standard-of-care therapy (69.5%), with a corresponding hazard ratio of 0.42 (P<0.0001). This result was consistent across key subgroups, including high-risk subgroups, such as patients with unmutated IGHV (HR 0.24) or del(q11) (HR 0.21). The safety analysis did not reveal surprising safety issues. Zanubrutinib was associated with fewer grade 3 adverse events (AEs) than standard-of-care (52.5% vs 79.7%). Moreover, treatment with zanubrutinib led to fewer AE-related dose reductions (7.5%) or discontinuations (8.3%) than the standard-of-regimen (37.4%; 13.7%).

Prof. Tam added that the results in cohort 2 of the SEQUOIA trial, those with del(17p), displayed similar results for patients who are treated with zanubrutinib. The PFS in this population is 88.9% at 24 months.

In conclusion, zanubrutinib showed encouraging efficacy and safety results as a first-line therapy for patients with treatment-naïve CLL/SLL, with consistency across relevant subgroups.

  1. Tam CS, 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). Abstract 396, ASH 2021 Annual Meeting, 11–14 December.
  2. Tam CS, et al. Blood. 2020;136(18):2038–2050.
  3. Hillmen P, et al. LB1900, EHA 2021 Congress, 9–17 June.


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