دورية أكاديمية
Mutational profile in previously treated patients with chronic lymphocytic leukemia progression on acalabrutinib or ibrutinib.
| العنوان: | Mutational profile in previously treated patients with chronic lymphocytic leukemia progression on acalabrutinib or ibrutinib. |
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| المؤلفون: | Woyach JA; The Ohio State University Comprehensive Cancer Center, Columbus, OH., Jones D; The Ohio State University Comprehensive Cancer Center, Columbus, OH.; Department of Pathology, The Ohio State University, Columbus, OH., Jurczak W; Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland., Robak T; Medical University of Lodz, and Copernicus Memorial Hospital, Lodz, Poland., Illés Á; Division of Hematology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Kater AP; Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam, on behalf of HOVON, Amsterdam, The Netherlands., Ghia P; Università Vita-Salute San Raffaele, Milan, Italy.; Division of Experimental Oncology, IRCCS Ospedale San Raffaele, Milan, Italy., Byrd JC; Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH., Seymour JF; Peter MacCallum Cancer Centre, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia., Long S; The Ohio State University Wexner Medical Center James Molecular Laboratory, Columbus, OH., Mohamed N; Department of Pathology, The Ohio State University, Columbus, OH., Benrashid S; The Ohio State University Comprehensive Cancer Center, Columbus, OH., Lai TH; The Ohio State University Comprehensive Cancer Center, Columbus, OH., De Jesus G; AstraZeneca, South San Francisco, CA., Lai R; AstraZeneca, South San Francisco, CA., de Bruin G; Acerta Pharma BV, a member of the AstraZeneca group, Oss, The Netherlands., Rule S; AstraZeneca, Mississauga, ON, Canada., Munugalavadla V; AstraZeneca, South San Francisco, CA. |
| المصدر: | Blood [Blood] 2024 Sep 05; Vol. 144 (10), pp. 1061-1068. |
| نوع المنشور: | Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | Adenine*/analogs & derivatives , Agammaglobulinaemia Tyrosine Kinase*/genetics , Agammaglobulinaemia Tyrosine Kinase*/antagonists & inhibitors , Benzamides*/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell*/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell*/genetics , Mutation* , Piperidines*/therapeutic use , Pyrazines*/therapeutic use , Pyrazines*/administration & dosage , Pyrazoles*/therapeutic use , Pyrimidines*/therapeutic use , Pyrimidines*/administration & dosage, Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Disease Progression ; Protein Kinase Inhibitors/therapeutic use ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/administration & dosage |
| مستخلص: | Abstract: Chronic 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. (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.) |
| References: | Blood. 2017 Mar 16;129(11):1469-1479. (PMID: 28049639) Blood. 2019 Aug 15;134(7):641-644. (PMID: 31243043) Blood. 2019 Mar 14;133(11):1205-1216. (PMID: 30602617) JCI Insight. 2019 Jun 20;4(12):. (PMID: 31217352) N Engl J Med. 2014 Jun 12;370(24):2352-4. (PMID: 24869597) J Clin Oncol. 2017 May 1;35(13):1437-1443. (PMID: 28418267) JAMA Oncol. 2015 Apr;1(1):80-7. (PMID: 26182309) Front Oncol. 2020 Jun 25;10:894. (PMID: 32670873) Blood Cancer J. 2022 May 20;12(5):80. (PMID: 35595730) N Engl J Med. 2014 Jun 12;370(24):2286-94. (PMID: 24869598) Blood Adv. 2023 Jun 27;7(12):2794-2806. (PMID: 36696464) Ther Adv Hematol. 2022 Aug 9;13:20406207221116577. (PMID: 35966045) Leukemia. 2021 May;35(5):1317-1329. (PMID: 33526860) Leukemia. 2017 Jul;31(7):1645-1647. (PMID: 28366935) Int J Cancer. 2020 Jan 1;146(1):85-93. (PMID: 31180577) Blood Adv. 2022 Oct 25;6(20):5589-5592. (PMID: 35901282) N Engl J Med. 2020 Jul 30;383(5):498-500. (PMID: 32726539) Blood. 2023 Jun 29;141(26):3137-3142. (PMID: 37156004) Immunity. 1995 May;2(5):451-60. (PMID: 7538439) Leukemia. 2021 Feb;35(2):312-332. (PMID: 33122850) N Engl J Med. 2022 Feb 24;386(8):735-743. (PMID: 35196427) Blood Adv. 2017 May 02;1(12):715-727. (PMID: 29296715) Oncotarget. 2017 Mar 14;8(11):17936-17944. (PMID: 28212557) J Clin Oncol. 2021 Nov 1;39(31):3441-3452. (PMID: 34310172) J Biol Chem. 1996 Nov 29;271(48):30303-6. (PMID: 8939985) |
| سلسلة جزيئية: | ClinicalTrials.gov NCT02477696 |
| المشرفين على المادة: | I42748ELQW (acalabrutinib) JAC85A2161 (Adenine) EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase) 0 (Benzamides) EC 2.7.10.2 (BTK protein, human) 1X70OSD4VX (ibrutinib) 0 (Piperidines) 0 (Protein Kinase Inhibitors) 0 (Pyrazines) 0 (Pyrazoles) 0 (Pyrimidines) |
| تواريخ الأحداث: | Date Created: 20240516 Date Completed: 20240905 Latest Revision: 20240919 |
| رمز التحديث: | 20240919 |
| مُعرف محوري في PubMed: | PMC11406168 |
| DOI: | 10.1182/blood.2023023659 |
| PMID: | 38754046 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
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| DOI: | 10.1182/blood.2023023659 |