TY - JOUR
T1 - The path forward for anti-programmed cell death-1 therapy in gliomas
AU - Majd, Nazanin
AU - Kamiya-Matsuoka, Carlos
AU - De Groot, John
N1 - Funding Information:
Editorial support was provided by Amy Ninetto in Scientific Publications Services, Research Medical Library, The University of Texas MD Anderson Cancer Center.
Publisher Copyright:
© 2019 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Purpose of review Checkpoint inhibitors (CPIs) represent the forefront of novel immunotherapeutic approaches for the treatment of solid cancers. However, the clinical development of CPIs in glioblastoma (GBM) has been challenging owing to an immunosuppressive tumor microenvironment and, possibly, low tumor mutation burden. Here, we review possible mechanisms responsible for the success of programmed cell death-1 (PD-1) blockade in patients with hypermutated GBM, recent clinical trials of anti-PD-1 monotherapy, trials incorporating neoadjuvant strategies, and trials of immunotherapy combination approaches in GBM. Mechanisms of resistance to immunotherapy and methods to overcome these challenges are also discussed. Recent findings Although two large phase III trials failed to demonstrate the superior efficacy of CPI in comparison with the standard of care in newly diagnosed and recurrent GBM, recent studies suggest that opportunities exist in some patients with GBM. A phase II study showed longer survival in patients with recurrent GBM who received neoadjuvant anti-PD-1 therapy than in those who received it as adjuvant therapy. In addition, cases of response to anti-PD-1 therapy in GBM patients with clonal hypermutator tumors have been reported. Summary Even though anti-PD-1 therapy does not seem to provide a benefit for molecularly unselected GBM patients, the success of PD-1 blockade in certain subsets of patients is encouraging.
AB - Purpose of review Checkpoint inhibitors (CPIs) represent the forefront of novel immunotherapeutic approaches for the treatment of solid cancers. However, the clinical development of CPIs in glioblastoma (GBM) has been challenging owing to an immunosuppressive tumor microenvironment and, possibly, low tumor mutation burden. Here, we review possible mechanisms responsible for the success of programmed cell death-1 (PD-1) blockade in patients with hypermutated GBM, recent clinical trials of anti-PD-1 monotherapy, trials incorporating neoadjuvant strategies, and trials of immunotherapy combination approaches in GBM. Mechanisms of resistance to immunotherapy and methods to overcome these challenges are also discussed. Recent findings Although two large phase III trials failed to demonstrate the superior efficacy of CPI in comparison with the standard of care in newly diagnosed and recurrent GBM, recent studies suggest that opportunities exist in some patients with GBM. A phase II study showed longer survival in patients with recurrent GBM who received neoadjuvant anti-PD-1 therapy than in those who received it as adjuvant therapy. In addition, cases of response to anti-PD-1 therapy in GBM patients with clonal hypermutator tumors have been reported. Summary Even though anti-PD-1 therapy does not seem to provide a benefit for molecularly unselected GBM patients, the success of PD-1 blockade in certain subsets of patients is encouraging.
KW - anti-programmed cell death-1 therapy
KW - checkpoint inhibitors
KW - glioblastoma
KW - immunosuppressive tumor microenvironment
KW - neoadjuvant checkpoint blockade
KW - tumor mutation burden
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U2 - 10.1097/WCO.0000000000000746
DO - 10.1097/WCO.0000000000000746
M3 - Review article
C2 - 31567548
AN - SCOPUS:85072634583
SN - 1350-7540
VL - 32
SP - 864
EP - 871
JO - Current Opinion in Neurology
JF - Current Opinion in Neurology
IS - 6
ER -