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Zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukemia and 17p deletion

Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have an unfavorable prognosis and respond poorly to standard chemoimmunotherapy. Zanubrutinib is a selective next-generation Bruton tyrosine kinase inhibitor. We eval...

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Autores principales: Tam, Constantine S., Robak, Tadeusz, Ghia, Paolo, Kahl, Brad S., Walker, Patricia, Janowski, Wojciech, Simpson, David, Shadman, Mazyar, Ganly, Peter S., Laurenti, Luca, Opat, Stephen, Tani, Monica, Ciepluch, Hanna, Verner, Emma, Šimkovič, Martin, Österborg, Anders, Trněný, Marek, Tedeschi, Alessandra, Paik, Jason C., Kuwahara, Sowmya B., Feng, Shibao, Ramakrishnan, Vanitha, Cohen, Aileen, Huang, Jane, Hillmen, Peter, Brown, Jennifer R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409041/
https://www.ncbi.nlm.nih.gov/pubmed/33054121
http://dx.doi.org/10.3324/haematol.2020.259432
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author Tam, Constantine S.
Robak, Tadeusz
Ghia, Paolo
Kahl, Brad S.
Walker, Patricia
Janowski, Wojciech
Simpson, David
Shadman, Mazyar
Ganly, Peter S.
Laurenti, Luca
Opat, Stephen
Tani, Monica
Ciepluch, Hanna
Verner, Emma
Šimkovič, Martin
Österborg, Anders
Trněný, Marek
Tedeschi, Alessandra
Paik, Jason C.
Kuwahara, Sowmya B.
Feng, Shibao
Ramakrishnan, Vanitha
Cohen, Aileen
Huang, Jane
Hillmen, Peter
Brown, Jennifer R.
author_facet Tam, Constantine S.
Robak, Tadeusz
Ghia, Paolo
Kahl, Brad S.
Walker, Patricia
Janowski, Wojciech
Simpson, David
Shadman, Mazyar
Ganly, Peter S.
Laurenti, Luca
Opat, Stephen
Tani, Monica
Ciepluch, Hanna
Verner, Emma
Šimkovič, Martin
Österborg, Anders
Trněný, Marek
Tedeschi, Alessandra
Paik, Jason C.
Kuwahara, Sowmya B.
Feng, Shibao
Ramakrishnan, Vanitha
Cohen, Aileen
Huang, Jane
Hillmen, Peter
Brown, Jennifer R.
author_sort Tam, Constantine S.
collection PubMed
description Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have an unfavorable prognosis and respond poorly to standard chemoimmunotherapy. Zanubrutinib is a selective next-generation Bruton tyrosine kinase inhibitor. We evaluated the safety and efficacy of zanubrutinib 160 mg twice daily in treatment-naïve patients with del(17p) disease enrolled in a dedicated, nonrandomized cohort (Arm C) of the phase III SEQUOIA trial. A total of 109 patients (median age, 70 years; range, 42–86) with centrally confirmed del(17p) were enrolled and treated. After a median of 18.2 months (range, 5.0–26.3), seven patients had discontinued study treatment due to progressive disease, four due to an adverse event, and one due to withdrawal of consent. The overall response rate was 94.5% with 3.7% of patients achieving complete response with or without incomplete hematologic recovery. The estimated 18-month progression-free survival rate was 88.6% (95% CI: 79.0–94.0) and the estimated 18-month overall survival rate was 95.1% (95% CI: 88.4–98.0). Most common all-grade adverse events included contusion (20.2%), upper respiratory tract infection (19.3%), neutropenia/ neutrophil count decreased (17.4%), and diarrhea (16.5%). Grade ≥3 adverse events were reported in 53 patients (48.6%), most commonly neutropenia (12.9%) and pneumonia (3.7%). An adverse event of atrial fibrillation was reported in three patients (2.8%). Zanubrutinib was active and well tolerated in this large, prospectively enrolled treatment cohort of previously untreated patients with del(17p) chronic lymphocytic leukemia/small lymphocytic lymphoma. This trial was registered as clinicaltrials.gov Identifier: NCT03336333.
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spelling pubmed-84090412021-09-08 Zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukemia and 17p deletion Tam, Constantine S. Robak, Tadeusz Ghia, Paolo Kahl, Brad S. Walker, Patricia Janowski, Wojciech Simpson, David Shadman, Mazyar Ganly, Peter S. Laurenti, Luca Opat, Stephen Tani, Monica Ciepluch, Hanna Verner, Emma Šimkovič, Martin Österborg, Anders Trněný, Marek Tedeschi, Alessandra Paik, Jason C. Kuwahara, Sowmya B. Feng, Shibao Ramakrishnan, Vanitha Cohen, Aileen Huang, Jane Hillmen, Peter Brown, Jennifer R. Haematologica Article Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have an unfavorable prognosis and respond poorly to standard chemoimmunotherapy. Zanubrutinib is a selective next-generation Bruton tyrosine kinase inhibitor. We evaluated the safety and efficacy of zanubrutinib 160 mg twice daily in treatment-naïve patients with del(17p) disease enrolled in a dedicated, nonrandomized cohort (Arm C) of the phase III SEQUOIA trial. A total of 109 patients (median age, 70 years; range, 42–86) with centrally confirmed del(17p) were enrolled and treated. After a median of 18.2 months (range, 5.0–26.3), seven patients had discontinued study treatment due to progressive disease, four due to an adverse event, and one due to withdrawal of consent. The overall response rate was 94.5% with 3.7% of patients achieving complete response with or without incomplete hematologic recovery. The estimated 18-month progression-free survival rate was 88.6% (95% CI: 79.0–94.0) and the estimated 18-month overall survival rate was 95.1% (95% CI: 88.4–98.0). Most common all-grade adverse events included contusion (20.2%), upper respiratory tract infection (19.3%), neutropenia/ neutrophil count decreased (17.4%), and diarrhea (16.5%). Grade ≥3 adverse events were reported in 53 patients (48.6%), most commonly neutropenia (12.9%) and pneumonia (3.7%). An adverse event of atrial fibrillation was reported in three patients (2.8%). Zanubrutinib was active and well tolerated in this large, prospectively enrolled treatment cohort of previously untreated patients with del(17p) chronic lymphocytic leukemia/small lymphocytic lymphoma. This trial was registered as clinicaltrials.gov Identifier: NCT03336333. Fondazione Ferrata Storti 2020-10-13 /pmc/articles/PMC8409041/ /pubmed/33054121 http://dx.doi.org/10.3324/haematol.2020.259432 Text en Copyright© 2021 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Tam, Constantine S.
Robak, Tadeusz
Ghia, Paolo
Kahl, Brad S.
Walker, Patricia
Janowski, Wojciech
Simpson, David
Shadman, Mazyar
Ganly, Peter S.
Laurenti, Luca
Opat, Stephen
Tani, Monica
Ciepluch, Hanna
Verner, Emma
Šimkovič, Martin
Österborg, Anders
Trněný, Marek
Tedeschi, Alessandra
Paik, Jason C.
Kuwahara, Sowmya B.
Feng, Shibao
Ramakrishnan, Vanitha
Cohen, Aileen
Huang, Jane
Hillmen, Peter
Brown, Jennifer R.
Zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukemia and 17p deletion
title Zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukemia and 17p deletion
title_full Zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukemia and 17p deletion
title_fullStr Zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukemia and 17p deletion
title_full_unstemmed Zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukemia and 17p deletion
title_short Zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukemia and 17p deletion
title_sort zanubrutinib monotherapy for patients with treatment-naïve chronic lymphocytic leukemia and 17p deletion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409041/
https://www.ncbi.nlm.nih.gov/pubmed/33054121
http://dx.doi.org/10.3324/haematol.2020.259432
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