Abstract
2033 Background: Treatment options for refractory high grade gliomas (HGG) are limited. Programmed cell death ligand-1 (PD-L1) expression has been reported in 0-61% of HGGs and therefore might be a suitable target in HGG. The purpose of this study was to describe safety and efficacy of PD-1 inhibition in patients with refractory HGGs. Methods: This IRB approved single center retrospective study at Memorial Sloan Kettering Cancer Center included pathologically confirmed HGG with an age ≥18 years who received a PD-1 inhibitor between 9/2014 and 10/2016 outside of a clinical trial. Results: Twenty five HGGs were identified. All patients received the PD-1 inhibitor pembrolizumab (pembro) as part of compassionate use. Median age was 49 years (range 30-72); 44% were men; 13 had glioblastoma (52%), 7 anaplastic astrocytoma (28%), 2 anaplastic oligodendroglioma (8%), 2 unspecified HGG (8%), and 1 gliosarcoma (4%). Patients received a median of 4 prior lines of therapy (range 1-9). Nineteen (76%) previously failed bevacizumab. Median baseline KPS was 80 (range 50-100). Concurrent treatment included bevacizumab in 17 (68%) or bevacizumab and temozolomide in 2 (8%) patients. Median number of doses administered was 3 (range 1-14). Treatment toxicity and response was assessed in 24 patients. PD-1 inhibitor related adverse events (AEs) included LFT elevations (33%), hypothyroidism (17%), diarrhea (17%), myalgias/arthralgias (13%), and rash (8%). Other common AEs were hyperglycemia, fatigue, thrombocytopenia, lymphopenia, headache, and nausea in the setting of concomitant therapy and additional supportive care (dexamethasone). Grade 3 AEs included seizure (4%), headache (4%), nausea (4%), and vomiting (4%). Best radiographic response was partial response (n = 2), stable disease (n = 5), and progressive disease (n = 17). Median progression free survival (PFS) was 42 days (range 7-282) and median overall survival was 121 days (range 15-415). Three patients (12%) had a PFS > 90 days; of these, 2 received single agent pembro. Conclusions: Patients with HGG had low response rates. However, a small number of patients had prolonged PFS. Pembro was tolerated with few serious AEs, even in patients receiving concomitant therapy.
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