Conclusions• Zantrene is highly effective at killing AML cells as a single agent across a diverse range of genetic subtypes both in vitro in cell culture and in vivo in mice.• The combination of Zantrene + decitabine shows strong synergy at a range of drug levels and AML genetic subtypes.• Dosing cells with decitabine as a single agent before dosing with Zantrene + decitabine provides improved synergy and cell killing in vitro.• Zantrene + decitabine are better able to kill human AML cells found in the bone marrow and spleen when using a mouse model of AML than using either drug alone.• The combination of Zantrene + decitabine causes regression of EMD AML tumours in a mouse model of extramedullary AML, further supporting the study of the combination Zantrene + decitabine in the clinic.• Results of this animal study will be rapidly translated to the clinic via a Race sponsored Phase 1b/2 trial of Zantrene + decitabine in patients with extramedullary AML or MDS, as well as part of a high intensity chemotherapy protocol in patient able and willing to tolerate such therapy.
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