ivosidenib + olutasidenib + enasidenib

This refers to the concurrent use of three oral small-molecule inhibitors of mutant isocitrate dehydrogenase (IDH) enzymes: ivosidenib (an IDH1 inhibitor), olutasidenib (an IDH1 inhibitor), and enasidenib (an IDH2 inhibitor). Ivosidenib (Tibsovo, developed by Agios and now marketed by Servier) and enasidenib (Idhifa, developed by Agios/Celgene/Bristol Myers Squibb) were the first targeted IDH1 and IDH2 inhibitors approved for relapsed or refractory acute myeloid leukemia (AML) with susceptible IDH1 or IDH2 mutations, and ivosidenib subsequently gained approvals in newly diagnosed AML (alone or with azacitidine), IDH1‑mutated cholangiocarcinoma, and IDH1‑mutated myelodysplastic syndromes.[1][2][4][6][8][10][12][13] Olutasidenib (Rezlidhia, developed by Forma and Rigel) is a later‑generation, selective IDH1 inhibitor approved for relapsed or refractory IDH1‑mutated AML, with activity associated with reduction of the oncometabolite (R)‑2‑hydroxyglutarate, restoration of normal cellular differentiation, and clinical remissions in this setting.[2][3][5][7][13] All three agents bind mutant IDH1 or IDH2 to inhibit production of 2‑hydroxyglutarate, relieve epigenetic repression, and promote differentiation of leukemic blasts; however, there is no established clinical regimen that intentionally combines all three together, and available data on IDH inhibitors largely concern each drug as monotherapy or in two‑drug combinations with chemotherapy or hypomethylating agents.[1][2][3][7][9][11][13]