Isocitrate dehydrogenase (IDH) 1/2 mutations occur in approximately 20% of older patients with acute myeloid leukemia (AML). Ivosidenib, an IDH1 inhibitor, is approved for the treatment of relapsed/refractory (R/R) IDH1mut AML and newly diagnosed (ND) patients ineligible for standard therapy, and enasidenib, an IDH2 inhibitor in IDH2mut R/R AML. In ND IDH1mut AML, ivosidenib offers complete remission (CR) plus CR with partial hematologic recovery (CRh) rate of 42% and median overall survival (OS) of 12.6 months, and in the R/R setting, CR/CRh of 30% and median OS of 8.8 months. 1 Comparably, enasidenib in ND IDH2mut AML patients showed a CR/CR with incomplete hematologic recovery (CRi) rate of 21% and median OS of 11.3 months, and in R/R patients, a CR/CRi of 26% and median OS of 8.8 months. 2

Venetoclax with hypomethylating agent (HMA) is now standard for elderly patients ineligible for intensive therapy. Preclinical studies have shown that IDH1/2mut primary AML cells are highly sensitive to BCL-2 inhibition which was confirmed by clinical studies showing durable responses in IDH1/2mut patients receiving venetoclax monotherapy. In the