Retrospective review of safety and efficacy of programmed cell death-1 inhibitors in refractory high grade gliomas Journal Article

   

Authors:	Reiss, S. N.; Yerram, P.; Modelevsky, L.; Grommes, C.
Article Title:	Retrospective review of safety and efficacy of programmed cell death-1 inhibitors in refractory high grade gliomas
Abstract:	Background: Programmed cell death ligand-1 (PD-L1) expression has been reported in up to 61% of high grade gliomas (HGG). The purpose of this study was to describe safety and efficacy of PD-1 inhibition in patients with refractory HGGs. Methods: This Institutional Review Board approved single center retrospective study included adult patients with pathologically confirmed HGG who received a PD-1 inhibitor from 9/2014-10/2016 outside of a clinical trial at Memorial Sloan Kettering Cancer Center. Results: Twenty five HGG patients received pembrolizumab as part of a compassionate use program. Median age was 50 years (range 30-72); 44% were men; 13 had glioblastoma (52%), 7 anaplastic astrocytoma (28%), 2 anaplastic oligodendroglioma (8%), 2 unspecified HGG (8%), and 1 gliosarcoma (4%). Median prior lines of treatments were 4 (range 1-9). Nineteen (76%) previously failed bevacizumab. Median KPS was 80 (range 50-100). Concurrent treatment included bevacizumab in 17 (68%) or bevacizumab and temozolomide in 2 (8%) patients. Median number of doses administered was 3 (range 1-14). Outcomes were assessed in 24 patients. PD-1 inhibitor related adverse events included LFT elevations, hypothyroidism, diarrhea, myalgias/arthralgias, and rash. Best radiographic response was partial response (n=2), stable disease (n=5), and progressive disease (n=17). Median progression free survival (PFS) was 1.4 months (range 0.2-9.4) and median overall survival (OS) was 4 months (range 0.5-13.8). Three-month PFS was 12% and 6-month OS was 28%. Conclusion: While response rates are low, a few patients had a prolonged PFS. Pembrolizumab was tolerated with few serious toxicities, even in patients receiving concomitant therapy. © 2017 The Author(s).
Keywords:	adult; clinical article; protein expression; aged; gene mutation; fatigue; neutropenia; bevacizumab; diarrhea; drug efficacy; drug safety; side effect; temozolomide; cancer staging; glioma; gene expression; anemia; leukopenia; mucosa inflammation; nausea; thrombocytopenia; vomiting; myalgia; dexamethasone; retrospective study; arthralgia; fever; hyperglycemia; rash; glioblastoma; oligodendroglioma; seizure; headache; hypothyroidism; astrocytoma; gliosarcoma; pd-1; programmed death 1 ligand 1; pd-l1; high-grade glioma; immune checkpoint; human; male; female; priority journal; article; pembrolizumab
Journal Title:	Journal for ImmunoTherapy of Cancer
Volume:	5
ISSN:	2051-1426
Publisher:	Biomed Central Ltd
Date Published:	2017-12-19
Start Page:	99
Language:	English
DOI:	10.1186/s40425-017-0302-x
PROVIDER:	scopus
PMCID:	PMC5735528
PUBMED:	29254497
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85038406958&doi=10.1186%2fs40425-017-0302-x&partnerID=40&md5=672b9d307da5e2245fcfc1ad29455597
Notes:	Article -- Export Date: 2 January 2018 -- Source: Scopus

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