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IDH2 Variant–Defined Subgroup Analysis of the Phase III IDHENTIFY Trial in AML

By: Julia Fiederlein
Posted: Wednesday, July 6, 2022

According to Stéphane De Botton, MD, PhD, of Gustave Roussy, Villejuif, France, and colleagues, mutational burden and co-mutational profiles differ between older patients with IDH2 R172– and R140–mutated relapsed or refractory acute myeloid leukemia (AML). This variant-defined subgroup analysis of the phase III IDHENTIFY trial, which was presented during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 7005), also revealed improved survival outcomes in those with the R172 variant allele who underwent salvage treatment with the IDH2 inhibitor enasidenib versus conventional care.

A total of 319 patients with IDH2 R172 (28%) or R140 (72%) mutations were randomly assigned in a 1:1 ratio to receive enasidenib or a conventional c-re regimen (azacitidine, intermediate- or low-dose cytarabine, or supportive care). Compared with the R172 subgroup, the R140 subgroup presented with a higher median number of baseline co-mutations (P < .0001). The most frequently co-occurring mutations were SRSF2 and RUNX1 (59% each) in the R140 subgroup and DNMT3A (57%) in the R172 subgroup. The R140 subgroup was enriched with SRSF2, FLT3, NPM1, RUNX1, and JAK2 mutations, whereas DNMT3A and TP53 mutations were more common in the R172 subgroup.

Based on a Cox multivariate analysis, compared with IDH2 R140 mutations, the R172 variant allele seemed to be significantly correlated with improved overall survival outcomes with enasidenib (P = .04); the number of baseline gene mutations was found to be significantly associated with overall survival with conventional care (P < .01). In the R172 subgroup, the median duration of overall survival was 14.6 months with enasidenib and 7.8 months with conventional care (P = .039); the 1-year survival rates were 62% and 30%, respectively. The median duration of overall survival was 5.7 months in both treatment arms of the R140 subgroup (P = .61); the 1-year survival rates were 29% and 25% with enasidenib and conventional care, respectively.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.


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