Cargando…

Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?

Treatment of cancer has transformed with the introduction of checkpoint inhibitors. However, the majority of solid tumor patients do not respond to checkpoint blockade. In contrast, the response rate to programmed cell death 1 (PD-1) blockade in relapsed/refractory classical Hodgkin lymphoma (cHL) i...

Descripción completa

Detalles Bibliográficos
Autores principales: Jeong, Ah-Reum, Ball, Edward D, Goodman, Aaron Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780174/
https://www.ncbi.nlm.nih.gov/pubmed/33447123
http://dx.doi.org/10.1177/1179554920976366
_version_ 1783631461933383680
author Jeong, Ah-Reum
Ball, Edward D
Goodman, Aaron Michael
author_facet Jeong, Ah-Reum
Ball, Edward D
Goodman, Aaron Michael
author_sort Jeong, Ah-Reum
collection PubMed
description Treatment of cancer has transformed with the introduction of checkpoint inhibitors. However, the majority of solid tumor patients do not respond to checkpoint blockade. In contrast, the response rate to programmed cell death 1 (PD-1) blockade in relapsed/refractory classical Hodgkin lymphoma (cHL) is 65% to 84% which is the highest among all cancers. Currently, checkpoint inhibitors are only approved for cHL and primary mediastinal B-cell lymphoma as the responses to single-agent checkpoint blockade in other hematologic malignancies is disappointingly low. Various established biomarkers such as programmed cell death 1 ligand 1 (PD-L1) protein surface expression, mismatch repair (MMR) status, and tumor mutational burden (TMB) are routinely used in clinical decision-making in solid tumors. In this review, we will explore these biomarkers in the context of hematologic malignancies. We review characteristic 9p24.1 structural alteration in cHL and primary mediastinal B-cell lymphoma (PMBCL) as a basis for response to PD-1 inhibition, as well as the role of antigen presentation pathways. We also explore the reported frequencies of MMR deficiency in various hematologic malignancies and investigate TMB as a predictive marker.
format Online
Article
Text
id pubmed-7780174
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher SAGE Publications
record_format MEDLINE/PubMed
spelling pubmed-77801742021-01-13 Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors? Jeong, Ah-Reum Ball, Edward D Goodman, Aaron Michael Clin Med Insights Oncol Review Article Treatment of cancer has transformed with the introduction of checkpoint inhibitors. However, the majority of solid tumor patients do not respond to checkpoint blockade. In contrast, the response rate to programmed cell death 1 (PD-1) blockade in relapsed/refractory classical Hodgkin lymphoma (cHL) is 65% to 84% which is the highest among all cancers. Currently, checkpoint inhibitors are only approved for cHL and primary mediastinal B-cell lymphoma as the responses to single-agent checkpoint blockade in other hematologic malignancies is disappointingly low. Various established biomarkers such as programmed cell death 1 ligand 1 (PD-L1) protein surface expression, mismatch repair (MMR) status, and tumor mutational burden (TMB) are routinely used in clinical decision-making in solid tumors. In this review, we will explore these biomarkers in the context of hematologic malignancies. We review characteristic 9p24.1 structural alteration in cHL and primary mediastinal B-cell lymphoma (PMBCL) as a basis for response to PD-1 inhibition, as well as the role of antigen presentation pathways. We also explore the reported frequencies of MMR deficiency in various hematologic malignancies and investigate TMB as a predictive marker. SAGE Publications 2020-12-28 /pmc/articles/PMC7780174/ /pubmed/33447123 http://dx.doi.org/10.1177/1179554920976366 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Review Article
Jeong, Ah-Reum
Ball, Edward D
Goodman, Aaron Michael
Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?
title Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?
title_full Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?
title_fullStr Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?
title_full_unstemmed Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?
title_short Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?
title_sort predicting responses to checkpoint inhibitors in lymphoma: are we up to the standards of solid tumors?
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780174/
https://www.ncbi.nlm.nih.gov/pubmed/33447123
http://dx.doi.org/10.1177/1179554920976366
work_keys_str_mv AT jeongahreum predictingresponsestocheckpointinhibitorsinlymphomaareweuptothestandardsofsolidtumors
AT balledwardd predictingresponsestocheckpointinhibitorsinlymphomaareweuptothestandardsofsolidtumors
AT goodmanaaronmichael predictingresponsestocheckpointinhibitorsinlymphomaareweuptothestandardsofsolidtumors