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Acalabrutinib Versus Investigator’s Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results

Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for patients with chronic lymphocytic leukemia (CLL). ASCEND is the pivotal phase 3 study of acalabrutinib versus investigator’s choice of idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) in patients with relapsed/refrac...

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Autores principales: Ghia, Paolo, Pluta, Andrzej, Wach, Małgorzata, Lysak, Daniel, Šimkovič, Martin, Kriachok, Iryna, Illés, Árpád, de la Serna, Javier, Dolan, Sean, Campbell, Philip, Musuraca, Gerardo, Jacob, Abraham, Avery, Eric J., Lee, Jae Hoon, Usenko, Ganna, Wang, Min Hui, Yu, Ting, Jurczak, Wojciech
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9666115/
https://www.ncbi.nlm.nih.gov/pubmed/36398134
http://dx.doi.org/10.1097/HS9.0000000000000801
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author Ghia, Paolo
Pluta, Andrzej
Wach, Małgorzata
Lysak, Daniel
Šimkovič, Martin
Kriachok, Iryna
Illés, Árpád
de la Serna, Javier
Dolan, Sean
Campbell, Philip
Musuraca, Gerardo
Jacob, Abraham
Avery, Eric J.
Lee, Jae Hoon
Usenko, Ganna
Wang, Min Hui
Yu, Ting
Jurczak, Wojciech
author_facet Ghia, Paolo
Pluta, Andrzej
Wach, Małgorzata
Lysak, Daniel
Šimkovič, Martin
Kriachok, Iryna
Illés, Árpád
de la Serna, Javier
Dolan, Sean
Campbell, Philip
Musuraca, Gerardo
Jacob, Abraham
Avery, Eric J.
Lee, Jae Hoon
Usenko, Ganna
Wang, Min Hui
Yu, Ting
Jurczak, Wojciech
author_sort Ghia, Paolo
collection PubMed
description Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for patients with chronic lymphocytic leukemia (CLL). ASCEND is the pivotal phase 3 study of acalabrutinib versus investigator’s choice of idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) in patients with relapsed/refractory (R/R) CLL. In the primary ASCEND analysis (median 16.1-month follow-up), acalabrutinib showed superior efficacy with an acceptable tolerability profile versus IdR/BR; here, we report final ~4 year follow-up results. Patients with R/R CLL received oral acalabrutinib 100 mg twice daily until progression or unacceptable toxicity, or investigator’s choice of IdR or BR. A total of 310 patients (acalabrutinib, n = 155; IdR, n = 119; BR, n = 36) were enrolled. At median follow-up of 46.5 months (acalabrutinib) and 45.3 months (IdR/BR), acalabrutinib significantly prolonged investigator-assessed progression-free survival (PFS) versus IdR/BR (median, not reached [NR] vs 16.8 months; P < 0.001); 42-month PFS rates were 62% (acalabrutinib) versus 19% (IdR/BR). Median overall survival (OS) was NR (both arms); 42-month OS rates were 78% (acalabrutinib) versus 65% (IdR/BR). Adverse events led to drug discontinuation in 23%, 67%, and 17% of patients in the acalabrutinib, IdR, and BR arms, respectively. Events of clinical interest (acalabrutinib vs IdR/BR) included all-grade atrial fibrillation/flutter (8% vs 3%), all-grade hypertension (8% vs 5%), all-grade major hemorrhage (3% vs 3%), grade ≥3 infections (29% vs 29%), and second primary malignancies excluding nonmelanoma skin cancer (7% vs 2%). At ~4 years follow-up, acalabrutinib maintained favorable efficacy versus standard-of-care regimens and a consistent tolerability profile in patients with R/R CLL.
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spelling pubmed-96661152022-11-16 Acalabrutinib Versus Investigator’s Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results Ghia, Paolo Pluta, Andrzej Wach, Małgorzata Lysak, Daniel Šimkovič, Martin Kriachok, Iryna Illés, Árpád de la Serna, Javier Dolan, Sean Campbell, Philip Musuraca, Gerardo Jacob, Abraham Avery, Eric J. Lee, Jae Hoon Usenko, Ganna Wang, Min Hui Yu, Ting Jurczak, Wojciech Hemasphere Article Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for patients with chronic lymphocytic leukemia (CLL). ASCEND is the pivotal phase 3 study of acalabrutinib versus investigator’s choice of idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) in patients with relapsed/refractory (R/R) CLL. In the primary ASCEND analysis (median 16.1-month follow-up), acalabrutinib showed superior efficacy with an acceptable tolerability profile versus IdR/BR; here, we report final ~4 year follow-up results. Patients with R/R CLL received oral acalabrutinib 100 mg twice daily until progression or unacceptable toxicity, or investigator’s choice of IdR or BR. A total of 310 patients (acalabrutinib, n = 155; IdR, n = 119; BR, n = 36) were enrolled. At median follow-up of 46.5 months (acalabrutinib) and 45.3 months (IdR/BR), acalabrutinib significantly prolonged investigator-assessed progression-free survival (PFS) versus IdR/BR (median, not reached [NR] vs 16.8 months; P < 0.001); 42-month PFS rates were 62% (acalabrutinib) versus 19% (IdR/BR). Median overall survival (OS) was NR (both arms); 42-month OS rates were 78% (acalabrutinib) versus 65% (IdR/BR). Adverse events led to drug discontinuation in 23%, 67%, and 17% of patients in the acalabrutinib, IdR, and BR arms, respectively. Events of clinical interest (acalabrutinib vs IdR/BR) included all-grade atrial fibrillation/flutter (8% vs 3%), all-grade hypertension (8% vs 5%), all-grade major hemorrhage (3% vs 3%), grade ≥3 infections (29% vs 29%), and second primary malignancies excluding nonmelanoma skin cancer (7% vs 2%). At ~4 years follow-up, acalabrutinib maintained favorable efficacy versus standard-of-care regimens and a consistent tolerability profile in patients with R/R CLL. Lippincott Williams & Wilkins 2022-11-14 /pmc/articles/PMC9666115/ /pubmed/36398134 http://dx.doi.org/10.1097/HS9.0000000000000801 Text en Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Ghia, Paolo
Pluta, Andrzej
Wach, Małgorzata
Lysak, Daniel
Šimkovič, Martin
Kriachok, Iryna
Illés, Árpád
de la Serna, Javier
Dolan, Sean
Campbell, Philip
Musuraca, Gerardo
Jacob, Abraham
Avery, Eric J.
Lee, Jae Hoon
Usenko, Ganna
Wang, Min Hui
Yu, Ting
Jurczak, Wojciech
Acalabrutinib Versus Investigator’s Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results
title Acalabrutinib Versus Investigator’s Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results
title_full Acalabrutinib Versus Investigator’s Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results
title_fullStr Acalabrutinib Versus Investigator’s Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results
title_full_unstemmed Acalabrutinib Versus Investigator’s Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results
title_short Acalabrutinib Versus Investigator’s Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results
title_sort acalabrutinib versus investigator’s choice in relapsed/refractory chronic lymphocytic leukemia: final ascend trial results
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9666115/
https://www.ncbi.nlm.nih.gov/pubmed/36398134
http://dx.doi.org/10.1097/HS9.0000000000000801
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