EXTH-08. IVOSIDENIB THERAPY FOR IDH-MUTANT WHO GRADE 4 ASTROCYTOMA

Abstract BACKGROUND Isocitrate Dehydrogenase (IDH) is a commonly mutated gene in gliomas, present in approximately 10% of high-grade gliomas. Its oncometabolite, D-2-hydroxyglutarate, has been implicated in promoting gliomagenesis and epileptogenesis. IDH-1 or IDH-2 mutations confer a more favorable prognosis in gliomas than wildtype IDH, leading to the differentiation between IDH-wild type glioblastoma and IDH-mutant WHO Grade 4 astrocytoma. Although IDH-mutant WHO Grade 4 astrocytomas tend to occur in younger patients and show an improved survival, prognosis remains poor and treatment options are limited. Ivosidenib is a small molecule inhibitor of IDH-1 that has shown promise for treating low-grade IDH-mutant glioma. However, little is known about its efficacy in IDH-mutant WHO Grade 4 astrocytoma. METHODS We present a retrospective case of a 38-year-old male with a WHO Grade 4 astrocytoma. Molecular characterization revealed that it was IDH-mutant, MGMTp methylated, and 1p/19q co-deleted. It was treated with ivosidenib at second recurrence. He was originally treated with gross total resection, followed by radiation and 6 cycles of adjuvant temozolomide. At the time of 1st progression (approximately 19 months postoperatively), he was treated with lomustine at 90mg/m2 but progressed after 2 cycles. Here we report the effects of off label use of ivosidenib. RESULTS Radiological surveillance showed interval decrease in tumor size starting two months after initiation of ivosidenib. The patient remained neurologically intact and no adverse effects were observed. A review of the literature revealed only three studies analyzing the effects of ivosidenib in IDH-mutated WHO Grade 4 astrocytomas with varying results. CONCLUSION The INDIGO trial published last year showed evidence of efficacy in using an IDH inhibitor for low-grade gliomas. The role of these drugs in high-grade IDH-mutated gliomas is currently unknown. Further studies are needed to assess their efficacy in overall and progression free survival, specifically in IDH-mutated WHO Grade 4 astrocytoma.