Metastatic Melanoma Patient Had a Complete Response with Clonal Expansion after Whole Brain Radiation and PD-1 Blockade

We report here on a patient with metastatic melanoma who had extensive brain metastases. After being treated with the sequential combination of whole brain radiation therapy followed by the PD-1-inhibitory antibody, pembrolizumab, the patient had a durable complete response. Retrospective laboratory...

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Bibliographic Details
Published in:Cancer immunology research 2017-02, Vol.5 (2), p.100-105
Main Authors: Haymaker, Cara L, Kim, DaeWon, Uemura, Marc, Vence, Luis M, Phillip, Ann, McQuail, Natalie, Brown, Paul D, Fernandez, Irina, Hudgens, Courtney W, Creasy, Caitlin, Hwu, Wen-Jen, Sharma, Padmanee, Tetzlaff, Michael T, Allison, James P, Hwu, Patrick, Bernatchez, Chantale, Diab, Adi
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal, Humanized - pharmacology
Antibodies, Monoclonal, Humanized - therapeutic use
Antineoplastic Agents, Immunological - therapeutic use
Biomarkers
Brain - diagnostic imaging
Brain - pathology
Brain Neoplasms - diagnosis
Brain Neoplasms - secondary
Brain Neoplasms - therapy
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Clonal Evolution - genetics
Combined Modality Therapy
Cranial Irradiation - methods
Female
Humans
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Lymphocyte Count
Lymphocytes, Tumor-Infiltrating - immunology
Magnetic Resonance Imaging
Melanoma - genetics
Melanoma - metabolism
Melanoma - pathology
Middle Aged
Programmed Cell Death 1 Receptor - antagonists & inhibitors
Treatment Outcome
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Summary:We report here on a patient with metastatic melanoma who had extensive brain metastases. After being treated with the sequential combination of whole brain radiation therapy followed by the PD-1-inhibitory antibody, pembrolizumab, the patient had a durable complete response. Retrospective laboratory studies of T cells revealed that, after treatment with anti-PD-1 commenced, effector CD8 T cells in the blood expanded and the ratio of CD8 :Treg T cells increased. A CD8 T-cell clone present in the initial brain metastases was expanded in the blood after anti-PD-1 treatment, which suggested an antitumor role for this clone. Immunohistochemical analysis confirmed the presence of CD8 T cells and low PD-L1 expression in the brain metastases before immunotherapy initiation. This sequence of therapy may provide an option for melanoma patients with unresponsive brain metastases. Cancer Immunol Res; 5(2); 100-5. ©2017 AACR.
ISSN:2326-6066
2326-6074
DOI:10.1158/2326-6066.CIR-16-0223