IMCT-18PD-1 INHIBITORS FOR RECURENT HIGH GRADE GLIOMA (HGG).

Treatment options for recurrent high grade gliomas (HGG) are limited. Programmed cell death-1 (PD-1) and its ligand PD-L1 are expressed in tumor lymphocytes and glioma cells and negatively regulate T-cell responses. PD-1 and PD-L1 inhibitors are under investigation in the treatment of various malignancies, and pembrolizumab and nivolumab are available for off-label use. We retrospectively reviewed records of patients treated with PD-1 inhibitors off-label for recurrent HGG and explored safety and efficacy. There were 12 patients (7 men), median age 54 (range 18-69). Diagnoses included anaplastic astrocytoma (AA, 2) or glioblastoma (GBM, 10). All patients received prior radiotherapy (RT) and temozolomide (TMZ). PD-1 directed therapy with pembrolizumab 2mg/kg every 3 weeks (11) or nivolumab 3m/kg every 2 weeks (1) was administered for 2nd (3), 3rd (4), or 4th (5) recurrence. All patients received concurrent therapy with pembrolizumab or nivolumab. Combinations included bevacizumab (bev, 3), bev + nitrosoureas (2), and bev + RT, bev + TMZ + RT, bev + hydroxyurea + RT, bev + imatinib, bev + Novo-TTF, RT alone, and TMZ alone (1 each). Five patients were receiving corticosteroids (dexamethasone, 1.0-8.0mg/day) at the initiation of PD-1 directed therapy. Toxicities known to be associated with PD-1 inhibitors including transaminitis (3), hypothyroidism (2), hyperthyroidism (1) and hyponatremia (1) were observed. One patient discontinued therapy due to toxicity. No toxicities unique to patients with central nervous system malignancies were seen. Best observed responses by Response Assessment in Neuro-Oncology criteria include partial response (2), stable disease (4) and progressive disease (6). Three patients with initial progressive disease may have had pseudoprogression, as follow-up imaging revealed stabilization, response, or unknown (1 each). Responders remain controlled with follow-up from 1.9-7.1 months. Survival data is immature and will be presented. PD-1 inhibitors can be administered safely to patients with HGG concurrently with other therapies including re-irradiation.