Eudocia Q Lee1,2,3. 1. Center for Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA. eqlee@partners.org. 2. Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA. eqlee@partners.org. 3. Harvard Medical School, Boston, MA, USA. eqlee@partners.org.
Abstract
PURPOSE: The purpose of this review is to summarize recent updates regarding immune checkpoint inhibitor therapy in GBM patients including updates in brain immunology, clinical trials, mechanisms of resistance, and biomarkers of response. METHODS: PubMed was searched to identify recent relevant articles on immune checkpoint inhibitor therapy as it pertains to GBM. Clinicaltrials.gov was also searched to identify relevant clinical trials. RESULTS: The reported randomized phase 2 and 3 clinical trials of immune checkpoint inhibitors (alone or in combination with standard therapy) have not demonstrated a survival benefit to date in either newly diagnosed or recurrent GBM. A small randomized surgical study of neoadjuvant and adjuvant pembrolizumab suggested an increase in PFS and OS compared to adjuvant pembrolizumab only; further studies are needed to validate this finding. CONCLUSIONS: Despite the positive impact of immune checkpoint inhibitors in many cancers, only a small subset of GBM patients respond to these agents. Further research is needed to identify biomarkers of response and therapies to rationally combine with immune checkpoint inhibitors.
PURPOSE: The purpose of this review is to summarize recent updates regarding immune checkpoint inhibitor therapy in GBM patients including updates in brain immunology, clinical trials, mechanisms of resistance, and biomarkers of response. METHODS: PubMed was searched to identify recent relevant articles on immune checkpoint inhibitor therapy as it pertains to GBM. Clinicaltrials.gov was also searched to identify relevant clinical trials. RESULTS: The reported randomized phase 2 and 3 clinical trials of immune checkpoint inhibitors (alone or in combination with standard therapy) have not demonstrated a survival benefit to date in either newly diagnosed or recurrent GBM. A small randomized surgical study of neoadjuvant and adjuvant pembrolizumab suggested an increase in PFS and OS compared to adjuvant pembrolizumab only; further studies are needed to validate this finding. CONCLUSIONS: Despite the positive impact of immune checkpoint inhibitors in many cancers, only a small subset of GBM patients respond to these agents. Further research is needed to identify biomarkers of response and therapies to rationally combine with immune checkpoint inhibitors.
Authors: Patrick Y Wen; Michael Weller; Eudocia Quant Lee; Brian M Alexander; Jill S Barnholtz-Sloan; Floris P Barthel; Tracy T Batchelor; Ranjit S Bindra; Susan M Chang; E Antonio Chiocca; Timothy F Cloughesy; John F DeGroot; Evanthia Galanis; Mark R Gilbert; Monika E Hegi; Craig Horbinski; Raymond Y Huang; Andrew B Lassman; Emilie Le Rhun; Michael Lim; Minesh P Mehta; Ingo K Mellinghoff; Giuseppe Minniti; David Nathanson; Michael Platten; Matthias Preusser; Patrick Roth; Marc Sanson; David Schiff; Susan C Short; Martin J B Taphoorn; Joerg-Christian Tonn; Jonathan Tsang; Roel G W Verhaak; Andreas von Deimling; Wolfgang Wick; Gelareh Zadeh; David A Reardon; Kenneth D Aldape; Martin J van den Bent Journal: Neuro Oncol Date: 2020-08-17 Impact factor: 12.300
Authors: Maryam Rahman; W Gregory Sawyer; Scott Lindhorst; Loic P Deleyrolle; Jeffrey K Harrison; Aida Karachi; Farhad Dastmalchi; Joseph Flores-Toro; Duane A Mitchell; Michael Lim; Mark R Gilbert; David A Reardon Journal: Neuro Oncol Date: 2020-09-29 Impact factor: 12.300
Authors: Pavlina Chuntova; Frances Chow; Payal B Watchmaker; Mildred Galvez; Amy B Heimberger; Evan W Newell; Aaron Diaz; Ronald A DePinho; Ming O Li; E John Wherry; Duane Mitchell; Masaki Terabe; Derek A Wainwright; Jay A Berzofsky; Christel Herold-Mende; James R Heath; Michael Lim; Kim A Margolin; E Antonio Chiocca; Noriyuki Kasahara; Benjamin M Ellingson; Christine E Brown; Yvonne Chen; Peter E Fecci; David A Reardon; Gavin P Dunn; Linda M Liau; Joseph F Costello; Wolfgang Wick; Timothy Cloughesy; William C Timmer; Patrick Y Wen; Robert M Prins; Michael Platten; Hideho Okada Journal: Neuro Oncol Date: 2021-03-25 Impact factor: 12.300
Authors: David A Reardon; Alba A Brandes; Antonio Omuro; Paul Mulholland; Michael Lim; Antje Wick; Joachim Baehring; Manmeet S Ahluwalia; Patrick Roth; Oliver Bähr; Surasak Phuphanich; Juan Manuel Sepulveda; Paul De Souza; Solmaz Sahebjam; Michael Carleton; Kay Tatsuoka; Corina Taitt; Ricardo Zwirtes; John Sampson; Michael Weller Journal: JAMA Oncol Date: 2020-07-01 Impact factor: 31.777
Authors: Moritz Klawitter; Ali El-Ayoubi; Jasmin Buch; Jakob Rüttinger; Maximilian Ehrenfeld; Eva Lichtenegger; Marcel A Krüger; Klaus Mantwill; Florestan J Koll; Markus C Kowarik; Per Sonne Holm; Ulrike Naumann Journal: Int J Mol Sci Date: 2022-09-01 Impact factor: 6.208