Abstract
Abstract INTRODUCTION: The standard chemotherapy for treating oligodendroglioma consists of a combination of procarbazine, lomustine, and vincristine (PCV). The combination of hypomethylating agents, like azacitidine, and BCL2 inhibitors like venetoclax have not been formally studied in the treatment of glial tumors. The combination of these two drugs is commonly used to treat acute myeloid leukemia, with IDH mutant disease being a particularly sensitive subtype. CASE REPORT: A 48-year-old man was diagnosed with a left frontal, grade II oligodendroglioma following multiple episodes of speech arrest and right-hand numbness. He was subsequently treated with six cycles of PCV with a minor response. After slow progression over eight years, the tumor started displaying contrast enhancement. While planning for radiation therapy, he presented to the Emergency Department with severe fatigue and shortness of breath. Workup led to a diagnosis of pure erythroid leukemia, with molecular and cytogenetic studies suggesting a neoplasm related to prior exposure to cytotoxic chemotherapy. He was treated with three cycles of venetoclax and azacitidine, but unfortunately, the erythroleukemia progressed after a transient response to this treatment. On the other hand, however, a re-staging MRI brain showed a remarkable reduction of his tumor size of approximately 40% per RANO criteria. The patient was off steroids and remained neurologically asymptomatic during this time. Discussion: The use of azacitidine for the treatment of IDH mutant gliomas has been reported in the literature, with mixed results that might suggest at least some benefit in a subtype of patients. Other studies have also suggested that the BCL2 gene is associated with treatment resistance and tumor recurrence in gliomas. Our case presents an interesting observation that combining a hypomethylating agent with a BCL2 inhibitor might convey clinical and radiographic benefits for patients with relapsed IDH mutant gliomas.
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