CTIM-18. FERUMOXYTOL MRI IN ASSESSING RESPONSE TO PEMBROLIZUMAB AND CHEMORADIATION IN PATIENTS WITH GRADE 4 GLIOMA

Abstract BACKGROUND Ferumoxytol, a blood pool contrast agent that enables ‘steady-state imaging’, which is not feasible with standard Gd-MRI. This open-label single-arm phase 2 trial (NCT03347617) evaluates the clinical utility of Ferumoxytol steady-state relative cerebral blood volume (Fe-SS rCBV) in differentiating true progression (TP) from Treatment Related Imaging Changes (TRIC) post-CRT in patients receiving the PD-1 inhibitor pembrolizumab concurrently with standard of care chemo-radiation following maximal safe resection in newly diagnosed glioblastoma. We hypothesize that TRIC will exhibit lower Fe-SS rCBV values due to the absence of neo-angiogenesis, typically associated with progressive high-grade glioma. METHODS Fifty-Six subjects with newly diagnosed histologically confirmed (WHO 2016) grade 4 glioma scheduled to start standard CRT followed by 6 cycles of adjuvant temozolomide (TMZ) were consented to receive upfront pembrolizumab (200 mg IV every 3 weeks starting +/- 10 days from start of CRT) and continued for up to two years, dose limiting toxicity or confirmed progression. Patients underwent Fe-MRI (early phase and 24-hour delayed phase) at four predetermined time points: 1. pre-radiation, 2. post-radiation, 3. suspected progression (SP), and 4. one-month post-SP. Clinical response (TP vs. TRIC) was assessed by biopsy or modified RANO criteria and correlated with Fe-SS-rCBV. Blood was collected at the study imaging time points for exploratory analysis. All Imaging processing has been completed. In this late-breaking abstract, we will present the (primary end point): longitudinal trend of Fe-SS-rCBV, sensitivity and specificity of Fe-SS-rCBV in distinguishing TP from TRIC in patients with newly diagnosed glioblastoma multiforme (GBM) receiving pembrolizumab with standard of care chemo-radiation. Secondary endpoints will include safety and tolerability, progression-free survival, and overall survival. Exploratory endpoints will include correlation of Fe-SS-rCBV and serum immunological parameters with clinical as well as radiological outcomes.