PATH-17. HYPERPROGRESSIVE DISEASE IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMAS TREATED WITH IMMUNE CHECKPOINT INHIBITORS OR CYTOTOXIC THERAPIES

Abstract

Abstract BACKGROUND Hyperprogressive disease (HPD), defined as a ≥ 2-fold increase in tumor growth rate (TGR) compared to baseline following initiation of immune checkpoint inhibitors (ICI), has been described in solid tumors but is not well explored high grade gliomas (HGG). We investigated the rate of HPD in HGG patients receiving ICIs for first or second recurrence compared to those treated with non-immunotherapy agents. METHODS Patients with HGG receiving ICIs for 1st or 2nd recurrence compared to a controls receiving other therapies at first progression. Prior or concurrent bevacizumab or anti-VEGFR were exclusionary due to pseudoresponse and decreased enhancement with these drugs. HPD was calculated by comparing TGR immediately before and after treatment. RESULTS 49 patients met inclusion criteria (27 ICI, 25 control). 25/27 patients receiving ICIs and 20/22 patients in the control group were evaluable in the analysis. The ICI group included 60% men (15/25) and 80% (20/25) had a diagnosis of primary GBM. 68% were treated at first progression (17/25). Controls were 80% male (16/20) and all had a diagnosis of primary GBM. 28% (7/25) of patients met criteria for HPD in the ICI group compared to 4/20 controls (20%). Median OS in patients with primary GBM was 26mo in the ICI group vs. 15.9mo in controls. Median survival past progression in patients with primary GBM receiving ICI for 1st recurrence (13/25) was 12mo vs. 10.6mo in controls. 40% of patients in both groups had next generation sequencing (5/7 with HPD in ICI and 2/4 in control). EGFR alterations and MDM2/4 amplifications were not associated with HPD whereas PTEN mutations were more common in HPD (71% vs. 33.3%). CONCLUSION HPD is observed in patients with HGG treated with ICI at comparable rates to those with other cancers, but was also observed in 20% of patients receiving other therapies.