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Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma

Polatuzumab vedotin, marketed under the trade name POLIVY(®), is a CD79b-targeted antibody-drug conjugate that preferentially delivers a potent anti-mitotic agent (monomethyl auristatin E) to B cells, resulting in anti-cancer activity against B-cell malignancies. In 2019, polatuzumab vedotin in comb...

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Autores principales: Dere, Randall C., Beardsley, Richard L., Lu, Dan, Lu, Tong, Ku, Grace H-W., Man, Gabriel, Nguyen, Van, Kaur, Surinder
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090561/
https://www.ncbi.nlm.nih.gov/pubmed/37063860
http://dx.doi.org/10.3389/fimmu.2023.1119510
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author Dere, Randall C.
Beardsley, Richard L.
Lu, Dan
Lu, Tong
Ku, Grace H-W.
Man, Gabriel
Nguyen, Van
Kaur, Surinder
author_facet Dere, Randall C.
Beardsley, Richard L.
Lu, Dan
Lu, Tong
Ku, Grace H-W.
Man, Gabriel
Nguyen, Van
Kaur, Surinder
author_sort Dere, Randall C.
collection PubMed
description Polatuzumab vedotin, marketed under the trade name POLIVY(®), is a CD79b-targeted antibody-drug conjugate that preferentially delivers a potent anti-mitotic agent (monomethyl auristatin E) to B cells, resulting in anti-cancer activity against B-cell malignancies. In 2019, polatuzumab vedotin in combination with rituximab and bendamustine was approved by the United States Food and Drug Administration for the treatment of adult patients with diffuse large B-cell lymphoma who have received at least two prior therapies. Recent Health Authority guidance recommendations for submitting an Integrated Summary of Immunogenicity were followed including a comprehensive immunogenicity risk assessment, bioanalytical strategy, and immunogenicity data to support the registration of polatuzumab vedotin. Key components of the polatuzumab vedotin Integrated Summary of Immunogenicity and data are presented. Validated semi-homogeneous bridging enzyme-linked immunosorbent assays were used to detect anti-drug antibodies (ADA) to polatuzumab vedotin and characterize the immune response in patients with non-Hodgkin’s lymphoma. The overall incidence of ADA observed for polatuzumab vedotin was low across seven clinical trials. The low incidence of ADA is likely due to the mechanism of action of polatuzumab vedotin that involves targeting and killing of B cells, thereby limiting the development to plasma cells and ADA secretion. Furthermore, patients are co-medicated with rituximab, which also targets B cells and results in B-cell depletion. Therefore, the immunogenicity risk is considered low and not expected to impact the polatuzumab vedotin benefit/risk profile.
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spelling pubmed-100905612023-04-13 Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma Dere, Randall C. Beardsley, Richard L. Lu, Dan Lu, Tong Ku, Grace H-W. Man, Gabriel Nguyen, Van Kaur, Surinder Front Immunol Immunology Polatuzumab vedotin, marketed under the trade name POLIVY(®), is a CD79b-targeted antibody-drug conjugate that preferentially delivers a potent anti-mitotic agent (monomethyl auristatin E) to B cells, resulting in anti-cancer activity against B-cell malignancies. In 2019, polatuzumab vedotin in combination with rituximab and bendamustine was approved by the United States Food and Drug Administration for the treatment of adult patients with diffuse large B-cell lymphoma who have received at least two prior therapies. Recent Health Authority guidance recommendations for submitting an Integrated Summary of Immunogenicity were followed including a comprehensive immunogenicity risk assessment, bioanalytical strategy, and immunogenicity data to support the registration of polatuzumab vedotin. Key components of the polatuzumab vedotin Integrated Summary of Immunogenicity and data are presented. Validated semi-homogeneous bridging enzyme-linked immunosorbent assays were used to detect anti-drug antibodies (ADA) to polatuzumab vedotin and characterize the immune response in patients with non-Hodgkin’s lymphoma. The overall incidence of ADA observed for polatuzumab vedotin was low across seven clinical trials. The low incidence of ADA is likely due to the mechanism of action of polatuzumab vedotin that involves targeting and killing of B cells, thereby limiting the development to plasma cells and ADA secretion. Furthermore, patients are co-medicated with rituximab, which also targets B cells and results in B-cell depletion. Therefore, the immunogenicity risk is considered low and not expected to impact the polatuzumab vedotin benefit/risk profile. Frontiers Media S.A. 2023-03-29 /pmc/articles/PMC10090561/ /pubmed/37063860 http://dx.doi.org/10.3389/fimmu.2023.1119510 Text en Copyright © 2023 Dere, Beardsley, Lu, Lu, Ku, Man, Nguyen and Kaur https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Dere, Randall C.
Beardsley, Richard L.
Lu, Dan
Lu, Tong
Ku, Grace H-W.
Man, Gabriel
Nguyen, Van
Kaur, Surinder
Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
title Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
title_full Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
title_fullStr Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
title_full_unstemmed Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
title_short Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
title_sort integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory b-cell non-hodgkin’s lymphoma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090561/
https://www.ncbi.nlm.nih.gov/pubmed/37063860
http://dx.doi.org/10.3389/fimmu.2023.1119510
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