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Zanubrutinib as frontline option independently of del(17p) and/or TP53 mut status

Updates on zanubrutinib monotherapy and combination with venetoclax in high-risk, treatment-naïve CLL/SLL from the SEQUOIA study1,2



The arm C and arm D from SEQUOIA continued to show the efficacy and tolerability of zanubrutinib monotherapy and combo with venetoclax regardless of the risk status in patients with treatment-naive CLL/SLL.1,2


Read SEQUOIA Arm C poster
from Shadman et al.1


Read SEQUOIA Arm D poster
from Shadman et al.2

How does zanubrutinib compare to acalabrutinib + venetoclax in low-risk, treatment-naive CLL?

In the absence of head-to-head trials, we used two distinct statistical analyses, a network meta-analysis (NMA) and a matching-adjusted indirect comparison (MAIC), to indirectly evaluate these treatments.3,4


Both methods identified a statistically significant improvement in PFS for zanubrutinib vs acalabrutinib + venetoclax in low-risk treatment-naive CLL.3,4


Read the NMA poster
from Shadman et al.3


Read the MAIC analysis poster
from Munir et al.4

How many cardiac deaths might be avoided from using zanubrutinib instead of ibrutinib?

Modelling analyses to estimate the number of ibrutinib-avoidable cardiac deaths in 1L and 2L+ CLL settings.5


Consider how switching from ibrutinib to zanubrutinib for CLL treatment may avoid cardiac deaths in 1L and 2L+ settings.5


Read the heart risk analysis
poster from Munir et al.5


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1L: first line; 2L+: second line or later; AF: atrial fibrillation; BR: Bendamustine + rituximab; CLL: chronic lymphocytic leukemia; FRC: Fludarabine + cyclophosphamide + rituximab; IGHV: immunoglobulin heavy chain; MAIC: matching-adjusted indirect comparison; MRD: minimal residual disease; NMA: network meta-analysis; NNH: number needed to harm; ORR: overall response rate; OS: overall survival; PFS: progression-free survival; PB: peripheral blood; SLL: small lymphocytic lymphoma; TEAEs: treatment-emergent adverse events; TLS: tumour lysis syndrome; uMRD: undetectable minimal residual disease; uMRD4: uMRD at <10-4 sensitivity (less than 1 CLL cell per 10 000 leukocytes).

  1. Shadman, M. et al. SEQUOIA 5-Year Follow-Up in Arm C: Frontline Zanubrutinib Monotherapy in Patients With del(17p) and Treatment-Naive Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Poster Presentation 1419 at the iwCLL; 12–15 Sep 2025; Kraków, Poland.
  2. Shadman, M. et al. Combination of Zanubrutinib + Venetoclax for Treatment-Naive Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Results in SEQUOIA Arm D. Poster Presentation 1420 at the iwCLL; 12–15 Sep 2025; Kraków, Poland.
  3. Shadman, M. et al. A Network Meta-Analysis (NMA) of Efficacy of Zanubrutinib versus Fixed-Duration Acalabrutinib Plus Venetoclax in Treatment-Naïve (TN) Chronic Lymphocytic Leukemia (CLL). Poster Presentation 1909 at the iwCLL; 12–15 Sep 2025; Kraków, Poland.
  4. Munir, T. et al. Comparative Efficacy of Zanubrutinib Versus Fixed-Duration Acalabrutinib Plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL): A Matching-Adjusted Indirect Comparison (MAIC). Poster Presentation 1910 at the iwCLL; 12–15 Sep 2025; Kraków, Poland.
  5. Munir, T. et al. Estimating the Cardiac Deaths Associated With Treating Chronic Lymphocytic Leukemia With Ibrutinib Versus Zanubrutinib in the United States. Poster Presentation 1528 at the iwCLL; 12–15 Sep 2025; Kraków, Poland.

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