RARE-37. TREATMENT OF H3K27M MUTANT GLIOMAS WITH PANOBINOSTAT

Abstract

Panobinostat (PBST) is a histone deacetylase inhibitor with biologic rationale in the treatment of gliomas harboring H3 K27M mutation. We performed a retrospective medical record review of adult patients with H3 K27M mutant diffuse midline glioma treated with PBST at Mayo Clinic (Rochester, MN). Four patients were identified with a mean age 40 years (range 22–62 years). Tumor location was: spinal cord (thoracic n=1, cervical n=1), brainstem (n=1), and thalamus (n=1).Two patients underwent biopsy alone while two underwent a partial resection. Three patients were treated with radiation (36–54 Gy) immediately prior to PBST monotherapy, and one patient was treated with PBST monotherapy without preceding radiation. All patients were otherwise chemotherapy naïve and did not receive any concurrent chemotherapy with PBST. PBST was dosed at either 10 mg (n=1) or 20mg (n=3) administered on days 1, 3, 5, 8, 10 and 12 of 21 day cycles. The mean duration of PBST therapy was 5 months (range 2–11 months). PBST was well tolerated overall. One patient experienced an objective response per RANO criteria. Two patients continue on therapy (5 cycles, 12 cycles) with stable disease. One patient rapidly progressed after 2 cycles of PBST therapy. In contrast with the patients who derived benefit from PBST, this patient was younger (22) and had multifocal disease with leptomeningeal involvement at treatment onset. The average progression free survival post PBST initiation was 8 months. This single institution case series shows promise that PBST may have therapeutic benefit in adult patients with H3 K27M mutant diffuse midline glioma.