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PD-1 expression and clinical PD-1 blockade in B-cell lymphomas.

Publication ,  Journal Article
Xu-Monette, ZY; Zhou, J; Young, KH
Published in: Blood
January 4, 2018

Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1+ tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials. The median duration of response was 16 months in a phase 2 trial. PD-1 blockade has also shown promise in a phase 1 trial of nivolumab in relapsed/refractory B-cell non-Hodgkin lymphomas, including follicular lymphoma, which often displays abundant PD-1 expression on intratumoral T cells, and diffuse large B-cell lymphoma, which variably expresses PD-1 and PD-L1. In primary mediastinal large B-cell lymphoma, which frequently has 9p24.1 alterations, the ORR was 35% in a phase 2 trial of pembrolizumab. In contrast, the ORR with pembrolizumab was 0% in relapsed chronic lymphocytic leukemia (CLL) and 44% in CLL with Richter transformation in a phase 2 trial. T cells from CLL patients have elevated PD-1 expression; CLL PD-1+ T cells can exhibit a pseudo-exhaustion or a replicative senescence phenotype. PD-1 expression was also found in marginal zone lymphoma but not in mantle cell lymphoma, although currently anti-PD-1 clinical trial data are not available. Mechanisms and predictive biomarkers for PD-1 blockade immunotherapy, treatment-related adverse events, hyperprogression, and combination therapies are discussed in the context of B-cell lymphomas.

Duke Scholars

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

January 4, 2018

Volume

131

Issue

1

Start / End Page

68 / 83

Location

United States

Related Subject Headings

  • Programmed Cell Death 1 Receptor
  • Lymphoma, B-Cell
  • Immunology
  • Humans
  • B7-H1 Antigen
  • Antibodies, Monoclonal
  • Animals
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xu-Monette, Z. Y., Zhou, J., & Young, K. H. (2018). PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood, 131(1), 68–83. https://doi.org/10.1182/blood-2017-07-740993
Xu-Monette, Zijun Y., Jianfeng Zhou, and Ken H. Young. “PD-1 expression and clinical PD-1 blockade in B-cell lymphomas.Blood 131, no. 1 (January 4, 2018): 68–83. https://doi.org/10.1182/blood-2017-07-740993.
Xu-Monette ZY, Zhou J, Young KH. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood. 2018 Jan 4;131(1):68–83.
Xu-Monette, Zijun Y., et al. “PD-1 expression and clinical PD-1 blockade in B-cell lymphomas.Blood, vol. 131, no. 1, Jan. 2018, pp. 68–83. Pubmed, doi:10.1182/blood-2017-07-740993.
Xu-Monette ZY, Zhou J, Young KH. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood. 2018 Jan 4;131(1):68–83.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

January 4, 2018

Volume

131

Issue

1

Start / End Page

68 / 83

Location

United States

Related Subject Headings

  • Programmed Cell Death 1 Receptor
  • Lymphoma, B-Cell
  • Immunology
  • Humans
  • B7-H1 Antigen
  • Antibodies, Monoclonal
  • Animals
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology