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Combining the newest leukaemia drug class with the venetoclax backbone is producing remission rates in frontline NPM1 and KMT2A leukaemia that single agents never reached.
This combination adds a menin inhibitor, ziftomenib or revumenib, to venetoclax and azacitidine as frontline treatment for acute myeloid leukaemia driven by NPM1 mutation or KMT2A rearrangement. Menin inhibition forces the leukaemia cells to differentiate and lowers their dependence on the BCL-2 family, venetoclax kills the primed cells, and azacitidine sensitises both steps. Early cohorts of KOMET-007 with ziftomenib and of the BEAT-AML and SAVE studies with revumenib report composite remission rates in newly diagnosed patients that single agents never reached, and phase 3 registration trials are under way; the evidence is phase 1 and 2 so far. Differentiation syndrome and cytopenias are the management challenge. The pairing builds on the VIALE-A and AUGMENT-101 papers.
Revumenib proved that a transcriptional dependency, rather than a kinase, can be drugged in leukaemia, opening treatment for two genetic subgroups that together cover roughly a third of AML plus most infant ALL. It is now approved and is being combined with venetoclax-azacitidine and intensive chemotherapy in front-line trials. Single-agent remissions are often short without transplant.
VIALE-A turned a palliative regimen into one that produces remission in two-thirds of older AML patients and is now the reference treatment for anyone not fit for intensive chemotherapy. It shifted the field towards lower-intensity targeted combinations and opened the door to adding FLT3, IDH and menin inhibitors to the backbone. Cure remains uncommon and most patients relapse within two years.
Shares NPM1 mutation, KMT2A (MLL) rearrangement, Ziftomenib, Revumenib.
Shares NPM1 mutation, KMT2A (MLL) rearrangement, Ziftomenib, Revumenib.
Shares NPM1 mutation, AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation, KMT2A (MLL) rearrangement, Revumenib.
Shares NPM1 mutation, Ziftomenib, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Menin.
Shares NPM1 mutation, Ziftomenib, Revumenib, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia.
Shares AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation, Revumenib, Menin, Acute myeloid leukaemia.
Shares Ziftomenib, Revumenib, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Menin.
Shares Ziftomenib, Revumenib, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Menin.