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.

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.

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.

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.