Abstract Details

Title Accelerated progression of IDH mutant glioma after first recurrence

Topic Neuro-oncology

Presentation(s) S14 - Translational and Clinical Advances in Neuro-oncology (1:22 PM-1:33 PM)

Poster/Presentation
Number 003

Objective

As a basis for clinical trial design for IDH-targeting drugs, we sought to characterize the natural history and factors associated with clinical outcomes exclusively within the glioma subgroup defined by IDH1 and IDH2 mutations.

Background

Isocitrate dehydrogenase (IDH) mutant gliomas are a distinct subtype, reflected in WHO 2016 revised diagnostic criteria. These tumors have a unique nature and underlying biology but most historical outcomes are derived from mixed populations of both IDH-mutant and IDH wild-type gliomas.

Design/Methods

We retrospectively analyzed 275 IDH mutant glioma patients treated at our institution. Progression was determined using low-grade glioma RANO criteria. We calculated survival statistics with the Kaplan-Meier method and survival proportions were correlated with molecular, histologic and clinical factors.

Results

During a median follow-up of 6.4 years, 44 deaths (7.6%) and 149 first progression (PFS1) events (54.1%) were observed. Median PFS1 was 5.7 years (95% CI 4.7-6.4) and OS was 18.7 years (95% CI 12.2 years - not reached). Consistent with prior studies, we observed an association of grade, molecular diagnosis and treatment with PFS1. Following the first progressive episode, 79 second progression events occurred during a median follow-up period of 4.1 years. Median PFS following an initial progressive event (PFS2) was accelerated at 3.1 years (95% CI 2.1-4.1). PFS2 was a surrogate prognostic marker, identifying patients with poorer overall survival.

Conclusions We report outcomes in a large cohort of IDH mutant glioma, providing a well-characterized historical control population for future clinical trial design. Notably, the interval between first to second recurrence (PFS2 - 3.0 years) is shorter than time from diagnosis to first recurrence (PFS1 - 5.7 years), evidence that these tumors clinically degenerate from an indolent course to a fulminant malignant phase. Thus, PFS2 represents a relevant outcome for trials investigating drug efficacy at recurrence.

Authors/Disclosures
Julie J. Miller, MD, PhD (Massachusetts General Hospital) PRESENTER	Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier. Dr. Miller has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for npj Precision Oncology. The institution of Dr. Miller has received research support from NINDS. The institution of Dr. Miller has received research support from American Cancer Society - IRG Pilot Grant. The institution of Dr. Miller has received research support from Karyopharm. The institution of Dr. Miller has received research support from NCI. The institution of Dr. Miller has received research support from American Brain Tumor Association.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Tracy T. Batchelor, MD, MPH (Brigham and Women's Hospital)	Dr. Batchelor has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Up To Date, Inc. An immediate family member of Dr. Batchelor has received publishing royalties from a publication relating to health care. Dr. Batchelor has received publishing royalties from a publication relating to health care.
Isabel Arrillaga-Romany, MD (Mass General Hospital)	Dr. Arrillaga-Romany has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boehringer Ingelheim. The institution of Dr. Arrillaga-Romany has received research support from Astex Pharmaceuticals. The institution of Dr. Arrillaga-Romany has received research support from Gsk.
Daniel P. Cahill, MD, PhD (MGH Cancer Center)	Daniel P. Cahill, MD, PhD has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Advise Connect Inspire. Daniel P. Cahill, MD, PhD has received personal compensation in the range of $0-$499 for serving as a Consultant for German Accelerator. Daniel P. Cahill, MD, PhD has received personal compensation in the range of $0-$499 for serving as a Consultant for Incephalo. Daniel P. Cahill, MD, PhD has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific.

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