Functional cure with single agent olutasidenib in relapsed IDH1/NPM1 co-mutated AML.

Olutasidenib is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) that was recently approved by the US FDA for adult patients with relapsed or refractory acute myeloid leukemia (AML) harboring mutant IDH1. In the pivotal Phase II trial of olutasidenib, the median duration of complete response (CR) was 28.1 months. Here we report the first patient in the world to receive olutasidenib, for relapsed NPM1 and IDH1 co-mutated AML, who remains in continuous CR for over 7 years on olutasidenib monotherapy. We detail the clinical course as well as the pathologic and genomic evolution of the disease. Furthermore, using a novel single cell measurable residual disease assay and digital PCR and qPCR for the detection of IDH1 and NPM1 mutations, we found no evidence of residual detectable leukemia. To our knowledge, this is the first report of an AML patient functionally cured by IDH1 inhibitor monotherapy.