Evidence map›Paper›PMID 40203277›Full record

ArticleBlood advances2025

Comparative efficacy of Bruton tyrosine kinase inhibitors in high-risk relapsed/refractory CLL: a network meta-analysis.

Mazyar Shadman, Jennifer R Brown, Leyla Mohseninejad, Keri Yang, Heather Burnett, Binod Neupane, Rhys Williams, Nicole Lamanna, Susan M O'Brien, Alessandra Tedeschi and 1 more

Abstract readComparative StudyNetwork Meta-Analysis
In one paragraph

Article in Blood advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Mazyar ShadmanClinical Research Division, Fred Hutchinson Cancer Center and Hematology and Oncology Division, University of Washington, Seattle, WA.ORCID 0000-0002-3365-6562
Jennifer R BrownChronic Lymphocytic Leukemia Center, Division of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.ORCID 0000-0003-2040-4961
Leyla MohseninejadBeOne Medicines Ltd, Schiphol, The Netherlands.
Keri YangBeOne Medicines Ltd, San Mateo, CA.
Heather BurnettEvidera, Montreal, Canada.ORCID 0000-0003-1269-4276
Binod NeupaneEvidera, Montreal, Canada.
Rhys WilliamsBeOne Medicines Ltd, San Mateo, CA.
Nicole LamannaHematology/Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY.ORCID 0000-0003-3331-9491
Susan M O'BrienDivision of Hematology/Oncology, School of Medicine, University of California, Irvine, CA.
Alessandra TedeschiDepartment of Hematology, Azienda Socio Sanitaria Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Constantine S TamLymphoma Service, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.ORCID 0000-0002-9759-5017

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstractBruton tyrosine kinase inhibitors (BTKis) have led to changes in the treatment algorithm for patients with high-risk relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), defined based on the presence of genetic mutations. Given the lack of head-to-head trials comparing next-generation BTKis used to treat high-risk R/R disease, a network meta-analysis (NMA) was performed to estimate their relative efficacy. High-risk populations were defined based on the prespecified definitions within each trial, including patients with del(17p) and/or TP53 mutations in the ALPINE (n = 150) and ASCEND (n = 86) trials, and del(17p)/del(11q) in the ELEVATE-RR (n = 533) trial. Bayesian NMAs found zanubrutinib to be the most efficacious treatment for high-risk patients, with significantly reduced risk of progression or death compared with ibrutinib (hazard ratio [HR], 0.49; 95% credible interval [CrI], 0.31-0.78), acalabrutinib (HR, 0.55; 95% CrI, 0.32-0.94), and bendamustine + rituximab or idelalisib + rituximab (BR/IR; HR, 0.12; 95% CrI, 0.05-0.26). Differences in overall survival demonstrated a numerical trend favoring zanubrutinib (probability better than ≥80%) compared with ibrutinib (HR, 0.59; 95% CrI, 0.31-1.11), acalabrutinib (HR, 0.72; 95% CrI, 0.35-1.50), and BR/IR (HR, 0.65; 95% CrI, 0.23-1.75). Rates of response also demonstrated trends favoring zanubrutinib compared with acalabrutinib, with significant results compared with ibrutinib. The NMA suggests that the most efficacious BTKi for patients with high-risk R/R CLL is zanubrutinib.

Indexed as

Agammaglobulinaemia Tyrosine KinaseLeukemia, Lymphocytic, Chronic, B-CellProtein Kinase InhibitorsAdenineHumansPiperidinesPyrazolesPyrimidinesRecurrenceTreatment OutcomeTyrosine Kinase InhibitorsAdenineAgammaglobulinaemia Tyrosine KinaseBTK protein, humanibrutinibPiperidinesProtein Kinase InhibitorsPyrazolesPyrimidinesTyrosine Kinase Inhibitorszanubrutinib

Identifiers

PMID40203277
PMCPMC12180973

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.