Trial reportBlood2024
Mutational profile in previously treated patients with chronic lymphocytic leukemia progression on acalabrutinib or ibrutinib.
Trial report in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02477696 (A Randomized, Multicenter, Open-Label, Non-Inferiority, Phase III Study of Acalabrutinib), which is not on this map. Cited by 31 papers.
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.
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.
A Randomized, Multicenter, Open-Label, Non-Inferiority, Phase III Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Subjects With High Risk Chronic Lymphocytic Leukemia
Who cites it
31 citing papers in PubMed.
- Docirbrutinib is a pan-mutant BTK inhibitor and inhibits B-cell receptor signaling in chronic lymphocytic leukemia cells in preclinical and early clinical investigations.Blood cancer journal · 2026Trial
- Trial
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Current management of central nervous system involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma.International journal of hematology · 2026Review
- PLCG2 exon-skipped variants: insights into their potential role in chronic lymphocytic leukemia.Blood advances · 2026Article
- Stereoselective Covalent Targeting of BTK(C481S) and Kinases with β-Lactone Electrophiles.bioRxiv : the preprint server for biology · 2026Article
- Molecular Insights and Novel Therapies for Lymphoproliferative Disorders.International journal of molecular sciences · 2026Review
- A Comprehensive Review of the Role of Zanubrutinib for Patients with Chronic Lymphocytic Leukemia.Oncology and therapy · 2026Review
- Cyclin-Dependent Kinase 5 Contributes to Bruton's Tyrosine Kinase Inhibitor Resistance via the IRE1α/XBP1 Axis in Mantle Cell Lymphoma.Research square · 2026Article
- Single-Cell RNA-seq Analysis Reveals Distinct Tumor and Immunosuppressive T-Cell Phenotypes in Patients with CLL Treated with Ibrutinib.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Population Pharmacokinetic Modeling and Exposure-Response Analyses of Nemtabrutinib in Patients With Hematologic Malignancies.CPT: pharmacometrics & systems pharmacology · 2026Article
- When Targeted Therapy Falls Short: Unraveling Resistance Mechanisms in Chronic Lymphocytic Leukemia.Current hematologic malignancy reports · 2026Review
- Mechanisms of resistance to bruton's tyrosine kinase inhibitors: synergistic effects of tumor microenvironment regulation and signaling pathways.Annals of hematology · 2026Review
- BTK Inhibition in Hematology: From CLL/SLL to Emerging Applications Across B-Cell and Immune Disorders.Biomolecules · 2026Review
- Article
- Genes-first and phenotypes-first paths to treatment resistance in hematological malignancies.Cell death & disease · 2025Review
- Management of Relapsed and/or Refractory Chronic Lymphocytic Leukemia.Hematology/oncology clinics of North America · 2025Review
- Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice.Leukemia · 2025Review
- Covalent and Non-Covalent BTK Inhibition in Chronic Lymphocytic Leukemia Treatment.Current treatment options in oncology · 2025Review
- Resistance mechanisms and approach to chronic lymphocytic leukemia after BTK inhibitor therapy.Leukemia & lymphoma · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
abstractChronic lymphocytic leukemia (CLL) progression during Bruton tyrosine kinase (BTK) inhibitor treatment is typically characterized by emergent B-cell receptor pathway mutations. Using peripheral blood samples from patients with relapsed/refractory CLL in ELEVATE-RR (NCT02477696; median 2 prior therapies), we report clonal evolution data for patients progressing on acalabrutinib or ibrutinib (median follow-up, 41 months). Paired (baseline and progression) samples were available for 47 (excluding 1 Richter) acalabrutinib-treated and 30 (excluding 6 Richter) ibrutinib-treated patients. At progression, emergent BTK mutations were observed in 31 acalabrutinib-treated (66%) and 11 ibrutinib-treated patients (37%; median variant allele fraction [VAF], 16.1% vs 15.6%, respectively). BTK C481S mutations were most common in both groups; T474I (n = 9; 8 co-occurring with C481) and the novel E41V mutation within the pleckstrin homology domain of BTK (n = 1) occurred with acalabrutinib, whereas neither mutation occurred with ibrutinib. L528W and A428D comutations presented in 1 ibrutinib-treated patient. Preexisting TP53 mutations were present in 25 acalabrutinib-treated (53.2%) and 16 ibrutinib-treated patients (53.3%) at screening. Emergent TP53 mutations occurred with acalabrutinib and ibrutinib (13% vs 7%; median VAF, 6.0% vs 37.3%, respectively). Six acalabrutinib-treated patients and 1 ibrutinib-treated patient had emergent TP53/BTK comutations. Emergent PLCG2 mutations occurred in 3 acalabrutinib-treated (6%) and 6 ibrutinib-treated patients (20%). One acalabrutinib-treated patient and 4 ibrutinib-treated patients had emergent BTK/PLCG2 comutations. Although common BTK C481 mutations were observed with both treatments, patterns of mutation and comutation frequency, mutation VAF, and uncommon BTK variants varied with acalabrutinib (T474I and E41V) and ibrutinib (L528W and A428D) in this patient population. The trial was registered at www.clinicaltrials.gov as #NCT02477696.
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Registered trials
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 OpenQuestion graph.