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Meta-Analysis
. 2022 Jan;39(1):165-177.
doi: 10.1007/s12325-021-01977-3. Epub 2021 Dec 1.

Clinical and Molecular Features of Patients with Gliomas Harboring IDH1 Non-canonical Mutations: A Systematic Review and Meta-Analysis

Vincenzo Di Nunno  1 , Enrico Franceschi  2 , Alicia Tosoni  3 , Lidia Gatto  1 , Ilaria Maggio  1 , Raffaele Lodi  4   5 , Daniele Angelini  3 , Stefania Bartolini  3 , Alba Ariela Brandes  3
Affiliations
Meta-Analysis

Clinical and Molecular Features of Patients with Gliomas Harboring IDH1 Non-canonical Mutations: A Systematic Review and Meta-Analysis

Vincenzo Di Nunno et al. Adv Ther. 2022 Jan.

Abstract

Introduction: The canonical isocitrate dehydrogenase 1 R132 mutation (IDH1 R132) is the most frequent mutation among IDH-mutated gliomas. Non-canonical IDH1 mutations or IDH2 mutations are unusual and their clinical and biological role is still unclear.

Methods: We performed a systematic review and meta-analysis to assess the clinical role of IDH non-canonical mutations.

Results: Overall, we selected 13 of 3513 studies reporting data of 4007 patients with a diagnosis of grade 2 and grade 3 glioma including 3091 patients with a molecularly proven IDH1 or IDH2 mutation. Patients with non-canonical IDH1 mutations were younger and presented a higher DNA methylation level as compared to those with canonical IDH1 R132H alteration. The overall incidence of non-canonical IDH1 mutations was 7.9% (95% CI 5.4-10.7%) in patients with IDH-mutated gliomas. There was no statistical difference in terms of incidence between patients with grade 2 or grade 3 glioma. Patients with non-canonical IDH mutations had a lower rate of 1p19q codeletion (risk difference 31%, 95% CI 23-38%) and presented a significantly prolonged survival (pooled HR 0.47, 95% CI 0.28-0.81) as compared to those with IDH1 R132H mutation.

Conclusion: Non-canonical IDH1 mutations occur in 7.9% of IDH-mutated gliomas and identify a specific subgroup of patients with an improved survival despite a lower rate of 1p19q codeletion. Data about the type of IDH mutation should be collected in clinical practice and within interventional trials as this could be a critical variable for improved stratification and selection of patients.

Keywords: Glioma; IDH; Isocitrate dehydrogenases; Meta-analysis; Non-canonical mutations; Systematic review.

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