Would you consider adding Enasidinib to frontline combination therapy with HMA and Venetoclax in a patient with newly diagnosed AML with IDH2 mutation that is >75 or unfit for standard induction therapy?

This question raises an important treatment consideration, but I would probably not use triple agents at this stage given lack of maturity of clinical trials. Venetoclax has been quite effective in those who have IDH1 and IDH2 mutations (Chan SM et al Nat Med 2015; 21:178), so I would probably start with an HMA and venetoclax combination without the IDH inhibitor and save that for later if no response or later loss of response to the HMA/venetoclax combination . There have been reports of using venetoclax with IDH inhibitors without HMAs, but I believe this has been published only in abstract form. The concern about the triple regimen would be increased myelosuppression in someone >75 years old and the effects on tumor lysis/differentiation...