Gliomas harboring IDH mutations present therapeutic challenges due to their infiltrative nature and resistance to conventional treatments. IDH enzyme inhibitors target the production of oncometabolite d-2 hydroxyglutarate . This intervention may delay malignant progression to a higher grade and reduce treatment-related complications.
We database engines PubMed, ClinicalTrials.gov and Google Scholar to gather studies on efficacy and safety of mutant IDH inhibitors, ivosidenib and vorasidenib, in patients with IDH-mutant gliomas. These studies reported outcomes such as response rates, progression-free survival(PFS), overall survival, and adverse events(AE). Analysis was done using meta and metafor in R. I2 statistics were used to assess heterogeneity.
Eight studies met the inclusion criteria. The pooled objective response rate (ORR) was 13.7% (95% CI: 7.3–24.0%), with subgroup analysis showing a rate of 4.3%(95%CI:0.9-18.1%) in studies with >24weeks of follow up (k=2), and 18.4% (95%CI:9.7-32.1%) at ≤24 weeks (k = 5). For patients with non-enhancing gliomas the mean difference (MD) in PFS was 18.83 months (p = 0.0237), with subgroup analysis showing a greater mean difference in studies with >24 weeks of follow-up (MD = 24.78 months, 95% CI: 2.06–47.50, k = 2), while ≤24 weeks of follow-up (k = 1) reported a smaller, non-significant effect (MD = 7.52 months). For those with enhancing gliomas, the MD was 1.90 months (p < 0.0001). The pooled incidence of any AE was 89.9%. Serious AE were reported in 17.0% (95% CI: 7.9–33.0%), and grade ≥3 AEs occurred in 19.1% of patients (95% CI: 13.2–26.8%).
IDH-mutant enzyme inhibitors demonstrate modest efficacy in treatment of gliomas, with substantial disease stabilization and prolonged progression free survival in non-enhancing gliomas. However, their low response rates and frequent toxicities call for careful risk–benefit assessment.