To describe a patient who had a recurrent WHO  grade 4 IDH-mutant astrocytoma, treated with concurrent lonafarnib, a farnesyltransferase inhibitor (FTI), and temozolomide followed by lonafarnib monotherapy.

WHO grade 4 IDH-mutant astrocytoma carries better prognosis compared to glioblastoma. However, the overall survival is generally less than 5 years. FTIs cause alterations in the Ras/PI3K/AKT/Rheb/mTOR pathways that consequently induce cell cycle arrest and promote autophagy. Autophagy of the endoplasmic reticulum is also evident in IDH-mutant gliomas, it is mediated by 2-hydroxyglutarate and may lead to an unusual downregulation of phospholipid biosynthesis. Our aim is to show the excellent therapeutic result of FTI in a patient with recurrent IDH-mutant astrocytoma.    

We present a patient with IDH-mutant astrocytoma successfully treated with FTI under protocol 2004-0424 and achieved long-term survival.

A 33 year-old gentleman was initially diagnosed with a WHO grade 4 IDH-mutant astrocytoma of the left frontal lobe that was treated with chemoradiation with temozolomide, followed by 4 cycles of adjuvant temozolomide. He then had disease progression and was enrolled in a clinical trial for treatment with temozolomide with lonafarnib for 24 cycles, followed by lonafarnib monotherapy. He has been neurologically stable with no progression of disease for more than 15 years. Next generation sequencing demonstrated somatic mutations in IDH1 (R132H), ATRX, PLCG2 and TP53 genes, with stable MSI, and 3 mutations/Mb.

Farnesyltransferase inhibition may be a feasible option for combination treatment in patients with IDH mutant diffuse gliomas. Further studies are warranted for the use of FTIs in IDH mutant gliomas.