Do you offer enasidenib with azacitadine in AML with an IDH2 mutation for patients ineligible for intensive induction chemotherapy?

I typically do not give enasidenib with azacitidine upfront for patients with AML with IDH2 mutation and ineligible for intensive induction chemotherapy. Based on the results of the VIALE-A study (DiNardo et al, NEJM 2020), I usually give venetoclax with azacitidine to those patients. In addition to the overall study results, subset analysis showed an advantage of the combo over aza alone in the IDH mutated subpopulation. The lack of survival advantage in the AG221-AML-005 study further contributes to my recommendations in this setting.

I would not give this outside of a clinical trial. An interesting trial would be enasidenib added to azacitidine plus venetoclax (which I agree is now the standard based on VIALE A). The data upfront is dissuading, as are the Phase 3 IDHentify trial data which showed the absence of primary endpoint OS advantage in the relapsed setting. Some interesting early data with ivosedinib in IDH1 mutated AML suggests added benefit in combination with azacitidine plus venetoclax but still early.