This study was presented by Fieke Hoff and we analysed our Beat AML dataset for older newly diagnosed AML patients with IDH mutations in order to describe the prevalence and prognostic impact of IDH mutations in this population. This population has been studied a lot in younger patients but the IDH prevalence increases with older patients and this is the biggest dataset in the older population that we are aware of that has been done.

This study is a retrospective data analysis of the Beat AML master trial screening data from its inception in November 2016 into May 2023. In this analysis we looked at 1,023 patients with newly diagnosed AML 60 years or older and we found that 9.7% of the patients in this cohort had an IDH1 mutation and 18.9% of the patients had an IDH2 mutation. We also saw that these IDH mutations commonly occurred with DNMT3A, MPM1 and less commonly with TP53 and also that these patients mainly have normal karyotype.

In order to evaluate the impact of the IDH mutations in older adults the study focused on patients evaluable for outcomes treated with either low intensive treatments or intensive chemotherapy. The hazard ratio deaths for IDH1 mutated patients treated with a low intensive therapy with the addition of an IDH1 inhibitor was significantly lower than IDH1 mutated patients treated without an inhibitor. The presence of an IDH2 inhibitor did not change the survival outcomes in patients with IDH2 mutations. Again, to our knowledge, this is the largest retrospective study characterising the older IDH mutated patients and with IDH mutations in about 27% of the population this is pretty prevalent for our older populations.

IDH2 mutation was associated with a lower hazard ratio of death among patients with the lower intensive treatment which was not seen in the patients receiving the intensive chemotherapy. This high prevalence of IDH mutations suggests that IDH inhibitors used as a single agent or in combination with other low intensive therapies are an important class of drugs for this older patient population since the IDH inhibitors are very generally tolerated and these should be looked in further investigation for treatment of these older patients.