دورية أكاديمية
أعرض في EDS

Acalabrutinib plus venetoclax and rituximab in treatment-naive mantle cell lymphoma: 2-year safety and efficacy analysis.

التفاصيل البيبلوغرافية
العنوان: Acalabrutinib plus venetoclax and rituximab in treatment-naive mantle cell lymphoma: 2-year safety and efficacy analysis.
المؤلفون: Wang M; Department of Lymphoma/Myeloma, Division of Cancer Medicine, MD Anderson Cancer Center, The University of Texas, Houston, TX., Robak T; Department of Hematology, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, Poland., Maddocks KJ; Division of Hematology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH., Phillips T; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI., Smith SD; University of Washington/Fred Hutchinson Cancer Center, Seattle, WA., Gallinson D; Summit Medical Group, Florham Park, NJ., Calvo R; AstraZeneca, Gaithersburg, MD., Wun CC; AstraZeneca, South San Francisco, CA., Munugalavadla V; AstraZeneca, South San Francisco, CA., Jurczak W; Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland.
المصدر: Blood advances [Blood Adv] 2024 Sep 10; Vol. 8 (17), pp. 4539-4548.
نوع المنشور: Journal Article; Clinical Trial, Phase I
اللغة: English
بيانات الدورية: Publisher: American Society of Hematology Country of Publication: United States NLM ID: 101698425 Publication Model: Print Cited Medium: Internet ISSN: 2473-9537 (Electronic) Linking ISSN: 24739529 NLM ISO Abbreviation: Blood Adv Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Society of Hematology, [2016]-
مواضيع طبية MeSH: Lymphoma, Mantle-Cell*/drug therapy , Rituximab*/therapeutic use , Rituximab*/administration & dosage , Rituximab*/adverse effects , Sulfonamides*/therapeutic use , Sulfonamides*/administration & dosage , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use , Antineoplastic Combined Chemotherapy Protocols*/adverse effects , Pyrazines*/administration & dosage , Pyrazines*/therapeutic use , Pyrazines*/adverse effects , Benzamides*/therapeutic use , Benzamides*/administration & dosage , Benzamides*/adverse effects, Humans ; Middle Aged ; Male ; Aged ; Female ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage ; Bridged Bicyclo Compounds, Heterocyclic/adverse effects ; Aged, 80 and over ; Adult ; Treatment Outcome ; COVID-19/mortality ; SARS-CoV-2
مستخلص: Abstract: This phase 1b study evaluated safety and efficacy of acalabrutinib, venetoclax, and rituximab (AVR) in treatment-naive mantle cell lymphoma (TN MCL). Patients received acalabrutinib from cycle 1 until progressive disease (PD) or undue toxicity, rituximab for 6 cycles with maintenance every other cycle through cycle 24 or until PD, and venetoclax, beginning at cycle 2, for 24 cycles. Twenty-one patients were enrolled; 95.2% completed induction (6 AVR cycles) and 47.6% continued acalabrutinib maintenance. Thirteen (61.9%) patients had grade 3-4 adverse events (AEs), most commonly neutropenia (33.3%). Seven (33.3%) patients had COVID-19 infection (6 [28.6%] serious AEs and 5 [23.8%] deaths, all among unvaccinated patients). There was no grade ≥3 atrial fibrillation, ventricular tachyarrhythmias, major hemorrhages, or tumor lysis syndrome. Overall response rate (ORR) was 100% (95% CI, 83.9-100.0) with 71.4% complete response. With median follow-up of 27.8 months, median progression-free survival (PFS) and overall survival (OS) were not reached. PFS rates at 1 and 2 years were 90.5% (95% CI, 67.0-97.5) and 63.2% (95% CI, 34.7-82.0), respectively; both were 95% after censoring COVID-19 deaths. OS rates at 1 and 2 years were 95.2% (95% CI, 70.7-99.3) and 75.2% (95% CI, 50.3-88.9), respectively; both were 100% after censoring COVID-19 deaths. Overall, 87.5% of patients with available minimal residual disease (MRD) data achieved MRD negativity (10-6; next-generation sequencing) during treatment. AVR represents a chemotherapy-free regimen for TN MCL and resulted in high ORR and high rates of MRD negativity. The trial was registered at www.ClinicalTrials.gov as #NCT02717624.
(© 2024 by The American Society of Hematology. 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: Br J Haematol. 2024 Feb;204(2):487-491. (PMID: 37669920)
N Engl J Med. 2018 Mar 29;378(13):1211-1223. (PMID: 29590547)
J Pharmacol Exp Ther. 2023 Jan;384(1):173-186. (PMID: 36310034)
Lancet Oncol. 2022 Mar;23(3):406-415. (PMID: 35074072)
J Hematol Oncol. 2021 Oct 30;14(1):179. (PMID: 34717692)
Lancet. 2013 Apr 6;381(9873):1203-10. (PMID: 23433739)
Blood. 2010 Apr 22;115(16):3215-23. (PMID: 20032498)
Blood. 2021 Feb 18;137(7):877-887. (PMID: 33181832)
Cancers (Basel). 2022 Jun 30;14(13):. (PMID: 35804999)
Br J Haematol. 2016 Nov;175(3):410-418. (PMID: 27378674)
Blood. 2022 Sep 22;140(12):1378-1389. (PMID: 35737911)
J Clin Oncol. 2022 Jan 10;40(2):202-212. (PMID: 34797699)
Expert Rev Hematol. 2022 Mar;15(3):273-284. (PMID: 35168449)
J Clin Oncol. 2014 Sep 20;32(27):3059-68. (PMID: 25113753)
Leuk Lymphoma. 2018 May;59(5):1064-1072. (PMID: 28758825)
Front Oncol. 2019 Jan 07;8:645. (PMID: 30666297)
Hemasphere. 2022 Apr 08;6(5):e0711. (PMID: 35425889)
J Clin Oncol. 2022 Apr 10;40(11):1196-1205. (PMID: 35030036)
Blood. 2016 Dec 15;128(24):2808-2818. (PMID: 27697772)
Nat Rev Immunol. 2021 Apr;21(4):245-256. (PMID: 33723416)
Blood Adv. 2024 Sep 10;8(17):4539-4548. (PMID: 38781315)
J Med Virol. 2021 Feb;93(2):1099-1104. (PMID: 32776581)
Blood Adv. 2022 Jul 26;6(14):4122-4131. (PMID: 35561314)
Ann Oncol. 2017 Jul 1;28(suppl_4):iv62-iv71. (PMID: 28881919)
Blood. 2013 Oct 3;122(14):2412-24. (PMID: 23940282)
Blood Adv. 2022 Mar 8;6(5):1490-1498. (PMID: 34700344)
Br J Haematol. 2015 Mar;168(5):765-8. (PMID: 25284608)
سلسلة جزيئية: ClinicalTrials.gov NCT02717624
المشرفين على المادة: I42748ELQW (acalabrutinib)
N54AIC43PW (venetoclax)
4F4X42SYQ6 (Rituximab)
0 (Sulfonamides)
0 (Pyrazines)
0 (Benzamides)
0 (Bridged Bicyclo Compounds, Heterocyclic)
تواريخ الأحداث: Date Created: 20240523 Date Completed: 20240829 Latest Revision: 20240916
رمز التحديث: 20240916
مُعرف محوري في PubMed: PMC11399641
DOI: 10.1182/bloodadvances.2023012424
PMID: 38781315
قاعدة البيانات: MEDLINE
الوصف
تدمد:2473-9537
DOI:10.1182/bloodadvances.2023012424