Menin inhibitor + venetoclax + azacitidine
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.
KOMET-007 (ziftomenib) and BEAT-AML/SAVE (revumenib) triplets report composite remission rates above 80% in newly diagnosed NPM1-mutant or KMT2Ar AML in early cohorts; phase 3 registration trials are underway. Differentiation syndrome and cytopenias are the management challenge.
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.