The Role of Mutant IDH Inhibitors in the Treatment of Glioma.

in Current neurology and neuroscience reports by Vihang Nakhate, Aleksandra B Lasica, Patrick Y Wen

TLDR

  • The study looked at how a specific type of brain tumor called glioma is treated. They found that a new type of treatment called mIDH inhibitors can help some patients with glioma. The study also looked at how well this treatment works and if it should be used more often.

Abstract

The identification of isocitrate dehydrogenase (IDH) mutations has led to a transformation in our understanding of gliomas and has paved the way to a new era of targeted therapy. In this article, we review the classification of IDH-mutant glioma, standard of care treatment options, clinical evidence for mutant IDH (mIDH) inhibitors, and practical implications of the recent landmark INDIGO trial. In the phase 3 randomized placebo-controlled INDIGO trial, mIDH1/2 inhibitor vorasidenib increased progression-free survival among non-enhancing grade 2 IDH-mutant gliomas following surgery. This marks the first positive randomized trial of targeted therapy in IDH-mutant glioma, and led to the US Food and Drug Administration's approval of vorasidenib in August 2024 for grade 2 IDH-mutant glioma. Vorasidenib is a well-tolerated treatment that can benefit a subset of patients with IDH-mutant glioma. Targeting mIDH also remains a promising strategy for select groups of patients excluded from the INDIGO trial. Ongoing and future studies, including with new agents and with combination therapy approaches, may expand the benefit and unlock the potential of mIDH inhibitors.

Overview

  • The study focuses on the classification of isocitrate dehydrogenase (IDH) mutations in gliomas and the standard of care treatment options. It also reviews the clinical evidence for mutant IDH (mIDH) inhibitors and the practical implications of the recent landmark INDIGO trial. The primary objective of the study is to provide an overview of the current state of IDH-mutant glioma treatment and the potential of mIDH inhibitors in this field.

Comparative Analysis & Findings

  • The INDIGO trial compared the outcomes of non-enhancing grade 2 IDH-mutant gliomas treated with vorasidenib to those treated with placebo. The results showed that vorasidenib increased progression-free survival among these patients. This marks the first positive randomized trial of targeted therapy in IDH-mutant glioma and led to the US Food and Drug Administration's approval of vorasidenib for grade 2 IDH-mutant glioma. The study highlights the potential of mIDH inhibitors as a well-tolerated treatment option for a subset of patients with IDH-mutant glioma.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice. The INDIGO trial represents a major milestone in the development of targeted therapy for IDH-mutant glioma, and the US Food and Drug Administration's approval of vorasidenib marks a significant step forward in this field. The study also highlights the potential of mIDH inhibitors as a promising strategy for select groups of patients excluded from the INDIGO trial. Ongoing and future studies, including with new agents and with combination therapy approaches, may expand the benefit and unlock the potential of mIDH inhibitors.
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