دورية أكاديمية
Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial.
| العنوان: | Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial. |
|---|---|
| المؤلفون: | Dimopoulos, Meletios, Sanz, Ramon Garcia, Lee, Hui-Peng, Trneny, Marek, Varettoni, Marzia, Opat, Stephen, D'Sa, Shirley, Owen, Roger G., Cull, Gavin, Mulligan, Stephen, Czyz, Jaroslaw, Castillo, Jorge J., Motta, Marina, Siddiqi, Tanya, Gironella Mesa, Mercedes, Granell Gorrochategui, Miquel, Talaulikar, Dipti, Zinzani, Pier Luigi, Askari, Elham, Grosicki, Sebastian, Oriol, Albert, Rule, Simon, Kloczko, Janusz, Tedeschi, Alessandra, Buske, Christian, Leblond, Veronique, Trotman, Judith, Chan, Wai Y., Michel, Jan, Schneider, Jingjing, Tan, Ziwen, Cohen, Aileen, Huang, Jane, Tam, Constantine S. |
| بيانات النشر: | American Society of Hematology |
| سنة النشر: | 2021 |
| المجموعة: | RD&E Research Repository (Royal Devon and Exeter NHS Foundation Trust) |
| مصطلحات موضوعية: | Humans, Myeloid Differentiation Factor 88/genetics, Waldenstrom Macroglobulinemia/drug therapy/genetics, Piperidines, Pyrazoles/adverse effects, Pyrimidines/adverse effects |
| الوصف: | Patients with Waldenström macroglobulinemia (WM) lacking activating mutations in the MYD88 gene (MYD88WT) have demonstrated relatively poor outcomes to ibrutinib monotherapy, with no major responses reported in a phase 2 pivotal study. Zanubrutinib is a novel, selective Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target activity. The ASPEN study consisted of a randomized comparison of zanubrutinib and ibrutinib efficacy and safety in patients with WM who have the MYD88 mutation, as well as a separate cohort of patients without MYD88 mutation (MYD88WT) or with unknown mutational status who received zanubrutinib. Results from the latter single-arm cohort are reported herein. Efficacy endpoints included overall, major and complete (CR) or very good partial response (VGPR) rates, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Twenty-eight patients (23 relapsed/refractory; 5 treatment-naive) were enrolled, including 26 with centrally confirmed MYD88WT disease and 2 with unknown MYD88 mutational status. At a median follow-up of 17.9 months, 7 of 26 MYD88WT patients (27%) had achieved a VGPR and 50% a major response (partial response or better); there were no CRs. At 18 months, the estimated PFS and OS rates were 68% and 88%, respectively, while the median DOR had not been reached. Two patients discontinued zanubrutinib due to adverse events. Treatment-emergent hypertension, atrial fibrillation, and major hemorrhages were reported in 3, 1 and 2 patients (including 1 concurrent with enoxaparin therapy), respectively. Results of this substudy demonstrate that zanubrutinib monotherapy can induce high quality responses in patients with MYD88WT WM. This trial is registered on www.clinicaltrials.gov as NCT #03053440. ; The article is available via Open Access. Click on the 'Additional link' above to access the full-text. ; Not permitted |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/33284944Test/; Dimopoulos, M. et al. (2020) 'Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial.', Blood advances, 4(23), pp. 6009-6018. doi:10.1182/bloodadvances.2020003010.; https://rde.dspace-express.com/handle/11287/621842Test; Blood advances; PMC7724905 |
| DOI: | 10.1182/bloodadvances.2020003010 |
| الإتاحة: | https://doi.org/10.1182/bloodadvances.2020003010Test https://rde.dspace-express.com/handle/11287/621842Test |
| حقوق: | © 2020 by The American Society of Hematology. ; http://creativecommons.org/publicdomain/zero/1.0Test/ |
| رقم الانضمام: | edsbas.3FBC8EB5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1182/bloodadvances.2020003010 |
|---|