Response dynamics in IDH2 mutant AML patients treated with enasidenib. Mutational burden in IDH2 mutant (mIDH2) AML can vary between the clonal (A) or subclonal (B) presence of a mIDH2 allele. In virtually all patients, treatment with enasidenib strongly reduced 2-HG plasma levels. In spite of this near-universal effect on 2-HG, various response scenarios were observed. Some patients showed evidence of a clinical response, schematically depicted in response scenarios a and b as differentiation of blasts to mature neutrophils. Of those patients, some remained mIDH2⁺ (a), whereas others became mIDH2⁻ (b). A third group of patients did not attain a clinical response, schematically depicted as a continued predominance of blasts that are partly or completely mIDH2⁺ (c). This simplified figure only indicates the extreme situations of either CR or complete resistance. Professional illustration by Patrick Lane, ScEYEnce Studios.