EPID-16. A MULTI-CENTER, PROGRESSION-FREE SURVIVAL ANALYSIS IN IDH-MUTANT GLIOMAS WITH CDKN2A DELETION: IMPLICATIONS FOR PROGNOSIS AND CLINICAL TRIAL DESIGN

Abstract

Abstract Homozygous deletion of CDKN2A is an important predictor of poor prognosis in patients with IDH-mutant gliomas. The updated 2021 WHO classification now recognizes this alteration as sufficient for the designation of an astrocytoma, IDH-mutant, WHO Grade 4, which otherwise requires histological observation of necrosis or microvascular proliferation. While overall survival patterns associated with CDKN2A deletion have been well-described, we sought to characterize progression-free survival (PFS) in this patient population. Across three institutions (Massachusetts General Hospital, Boston; University Hospital Heidelberg, Heidelberg; TU Dresden, Dresden), we identified 48 patients with IDH-mutant gliomas in which CDKN2A deletion was detected at the time of diagnosis, followed for a median of 15.2 years. The average age of the cohort is 35 years, with 60% of the patients identified as male. Most patient received immediate treatment after surgery, with 81% of the cohort undergoing radiation therapy and 73% receiving chemotherapy. Based on RANO criteria, the median progression-free survival of this patient population is 2.8 years (95% CI 1.4 – 3.3 years) and median overall survival is 4.3 years (95% CI 2.1 – 6.6 years). A positive T2/FLAIR mismatch sign or lack of contrast enhancement on MRI at the time of diagnosis are both associated with improved PFS in univariate regression analysis. For comparison, we identified a control cohort of 51 patients with astrocytoma, IDH-mutant, grade 4 without CDKN2A deletion from MGH, achieving grade 4 by histologic criteria. Demographics were similar to the CDKN2A-deleted cohort, with median age (37 years) and percentage of male patients (60%). Notably, however, PFS for the grade 4, CDKN2A-intact, IDH-mutant glioma comparison group is estimated at 5.9 years (95% CI 3.3 – 7.9 years). Overall, these data reinforce the accelerated disease course associated with deletion of CDKN2A in IDH-mutant gliomas, providing an important reference for clinical trial design.