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Copanlisib for the Treatment of Malignant Lymphoma: Clinical Experience and Future Perspectives

Dysregulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin signaling is common in both indolent and aggressive forms of malignant lymphoma, for which several targeted therapies have been developed. Copanlisib is a highly selective and potent intravenous pan-...

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Autores principales: Munoz, Javier, Follows, George A., Nastoupil, Loretta J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941125/
https://www.ncbi.nlm.nih.gov/pubmed/33687623
http://dx.doi.org/10.1007/s11523-021-00802-9
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author Munoz, Javier
Follows, George A.
Nastoupil, Loretta J.
author_facet Munoz, Javier
Follows, George A.
Nastoupil, Loretta J.
author_sort Munoz, Javier
collection PubMed
description Dysregulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin signaling is common in both indolent and aggressive forms of malignant lymphoma, for which several targeted therapies have been developed. Copanlisib is a highly selective and potent intravenous pan-class I PI3K inhibitor that has demonstrated durable objective responses and a manageable safety profile in heavily pre-treated patients with indolent lymphomas. As a result, copanlisib monotherapy received accelerated approval from the US Food and Drug Administration for the treatment of adults with relapsed follicular lymphoma who have received at least two systemic therapies, and breakthrough designation for patients with pre-treated relapsed or refractory marginal zone lymphoma. Hyperglycemia and hypertension are among the most frequently reported adverse events with copanlisib monotherapy, and are infusion-related, transient, and manageable with standard therapies. Mild diarrhea is also a common adverse event with copanlisib monotherapy; there is no evidence of worsening severity of diarrhea, or serious gastrointestinal toxicities such as colitis or severe liver enzyme elevations, which have been reported with orally administered PI3K inhibitors. The intravenous route of administration and intermittent dosing schedule of copanlisib may support a favorable tolerability profile over continually administered oral alternatives. Ongoing studies of copanlisib in combination with rituximab and standard-of-care chemotherapy in patients with relapsed indolent lymphoma have the potential to support the use of copanlisib in the second-line setting, providing a much-needed additional therapeutic option in this underserved patient population.
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spelling pubmed-79411252021-03-09 Copanlisib for the Treatment of Malignant Lymphoma: Clinical Experience and Future Perspectives Munoz, Javier Follows, George A. Nastoupil, Loretta J. Target Oncol Review Article Dysregulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin signaling is common in both indolent and aggressive forms of malignant lymphoma, for which several targeted therapies have been developed. Copanlisib is a highly selective and potent intravenous pan-class I PI3K inhibitor that has demonstrated durable objective responses and a manageable safety profile in heavily pre-treated patients with indolent lymphomas. As a result, copanlisib monotherapy received accelerated approval from the US Food and Drug Administration for the treatment of adults with relapsed follicular lymphoma who have received at least two systemic therapies, and breakthrough designation for patients with pre-treated relapsed or refractory marginal zone lymphoma. Hyperglycemia and hypertension are among the most frequently reported adverse events with copanlisib monotherapy, and are infusion-related, transient, and manageable with standard therapies. Mild diarrhea is also a common adverse event with copanlisib monotherapy; there is no evidence of worsening severity of diarrhea, or serious gastrointestinal toxicities such as colitis or severe liver enzyme elevations, which have been reported with orally administered PI3K inhibitors. The intravenous route of administration and intermittent dosing schedule of copanlisib may support a favorable tolerability profile over continually administered oral alternatives. Ongoing studies of copanlisib in combination with rituximab and standard-of-care chemotherapy in patients with relapsed indolent lymphoma have the potential to support the use of copanlisib in the second-line setting, providing a much-needed additional therapeutic option in this underserved patient population. Springer International Publishing 2021-03-09 2021 /pmc/articles/PMC7941125/ /pubmed/33687623 http://dx.doi.org/10.1007/s11523-021-00802-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Review Article
Munoz, Javier
Follows, George A.
Nastoupil, Loretta J.
Copanlisib for the Treatment of Malignant Lymphoma: Clinical Experience and Future Perspectives
title Copanlisib for the Treatment of Malignant Lymphoma: Clinical Experience and Future Perspectives
title_full Copanlisib for the Treatment of Malignant Lymphoma: Clinical Experience and Future Perspectives
title_fullStr Copanlisib for the Treatment of Malignant Lymphoma: Clinical Experience and Future Perspectives
title_full_unstemmed Copanlisib for the Treatment of Malignant Lymphoma: Clinical Experience and Future Perspectives
title_short Copanlisib for the Treatment of Malignant Lymphoma: Clinical Experience and Future Perspectives
title_sort copanlisib for the treatment of malignant lymphoma: clinical experience and future perspectives
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941125/
https://www.ncbi.nlm.nih.gov/pubmed/33687623
http://dx.doi.org/10.1007/s11523-021-00802-9
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