Abstract Details

Title Clinical and Molecular Determinants of Survival Outcomes in Glioblastoma Patients Treated with Immune Checkpoint Inhibitors

Topic Neuro-oncology

Presentation(s) S27 - Innovations in Neuro-oncology (2:12 PM-2:24 PM)

Poster/Presentation
Number 007

Background Prognosis of GBM patients remains poor with current standard-of-care. CPIs have improved survival of patients with a variety of solid cancers; however, responses have only been seen in a small subset of GBM patients. The clinical and molecular determinants of response to CPIs in GBM remain elusive.

Objective To determine factors associated with outcomes in glioblastoma (GBM) patients treated with immune checkpoint inhibitors (CPI).

Design/Methods We identified 38 adult recurrent GBM patients who received treatment with an anti-PD-1 (Nivolumab or Pembrolizumab) or anti-CTLA-4 (Ipilimumab) therapy at MD Anderson from January 2015 to August 2019. We associated patients’ demographic, clinical, and molecular data with survival outcomes. Regression analyses of survival data based on the Cox proportional hazards model were conducted on PFS and OS in multivariate setting.

Results Patients who received steroids prior to CPI initiation had inferior OS from time of diagnosis compared to those who did not (HR=3.395 (1.729, 6.667), p=.0004). Similar association was not seen when steroids were administered after initiation of CPI. Length of CPI therapy (> 6mo vs. £ 6mo) was associated with improved PFS and OS; PFS HR=0.493 (0.327, 0.744), p=0.0007), OS HR=0.573 (0.383, 0.857), p=0.0068. Patients with IDH and PI3K mutations had inferior OS compared to patients with wild-type status from time of diagnosis and from time of CPI initiation, respectively (IDH mutation HR=15.4 (1.984, 119.518), p=0.0089, PI3K mutation HR=5.631 (1.843, 17.206), p=0.0024).

Conclusions

Baseline steroids may have a blunting effect on outcomes of GBM patients treated with CPIs. Interestingly, though IDH mutation is a favorable prognostic indicator in gliomas, in the setting of CPI treatment this may not hold, consistent with previously described increased suppression of T-cell-mediated antitumor activity in IDH mutant vs. wild-type gliomas. Given the small sample size and retrospective nature of this study, these conclusions need confirmation in larger studies.

Authors/Disclosures
Pushan R. Dasgupta, MD, PhD (UT Dell Medical School at Austin) PRESENTER	Dr. Dasgupta has nothing to disclose.
	No disclosure on file
Zaid A. Soomro, MBBS (The University of Texas MD Anderson Cancer Center)	Dr. Soomro has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
John F. De Groot, MD (UC San Francisco Medical Center)	An immediate family member of Dr. De Groot has received personal compensation for serving as an employee of Ziopharm Oncology. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Celldex. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Deciphera Pharmaceuticals. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AbbVie. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for FivePrime Therapeutics, Inc.. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GW Pharma. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Carthera. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kadmon. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Biomedical Inc.. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Taiho Pharmaceuticals. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kairos Venture Investments. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Syneos Health. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Monteris. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Agios. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mundipharma Research. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GenomiCare. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Blue Earth Diagnostics. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Del Mar Pharmaceuticals. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Insightec. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Voyager Therapeutics, Inc.. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck & Co.. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Tocagen. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bioasis Technologies, Inc.. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for ResTORbio, Inc.. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celldex. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Foundation Medicine, Inc.. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novogen. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Deciphera. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Astrazeneca. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Insys Therapeutics. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck & Co.. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lily. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novella Clinical. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Karyopharm Therapeutics. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Blue Earth Diagnostics. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kiyatec. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vanquish Oncology. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Orsenix, Insightec. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Prelude Therapeutics. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Debiopharm Therapeutics, Inc.. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen Global Services, LLC. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for VBL Therapeutics. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novella. Dr. De Groot has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for VBI Vaccines, Inc.. An immediate family member of Dr. De Groot has received stock or an ownership interest from Ziopharm Oncology. An immediate family member of Dr. De Groot has received stock or an ownership interest from Gilead. The institution of Dr. De Groot has received research support from Carthera. The institution of Dr. De Groot has received research support from HaiHe Pharma. The institution of Dr. De Groot has received research support from Taiho Pharma.
Nazanin K. Majd, MD	No disclosure on file