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

Frontiers in Immunology

Immunology

Richard L. Beardsley¹  Van Nguyen²  Surinder Kaur²  Randall C. Dere²  Tong Lu³  Dan Lu³  Grace H-W. Ku⁴  Gabriel Man⁵ 

[1] Department of Analytical Development and Quality Control, Genentech, Inc., South San Francisco, CA, United States;Department of BioAnalytical Sciences, Genentech, Inc., South, San Francisco, CA, United States;Department of Clinical Pharmacology Oncology, Genentech, Inc., South San Francisco, CA, United States;Department of Product Development Hematology, Genentech, Inc., South San Francisco, CA, United States;Department of Product Development Safety, Genentech, Inc., South San Francisco, CA, United States;

关键词: POLIVY;    polatuzumab vedotin;    antibody-drug conjugate;    integrated summary of immunogenicity;    diffuse large B- cell lymphoma;   

DOI  :  10.3389/fimmu.2023.1119510

 received in 2022-12-08, accepted in 2023-03-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Dere, Beardsley, Lu, Lu, Ku, Man, Nguyen and Kaur