Schematic presentation of the VAF changes of KIT D816V and additional mutations in 12 patients during treatment with midostaurin. Five clusters were identified (A-E): (A) Significant reduction of KIT D816V but without significant VAF changes of the additional mutations. All patients were maintained on midostaurin. (B) Significant reduction of KIT D816V but expansion of RUNX1 (#12) or NRAS (#02) with subsequent disease progression and death (in #12 after progression into secondary acute myeloid leukemia). (C) Significant increase of KIT D816V but stable VAF of additional mutations with subsequent disease progression and death. (D) Significant increase of KIT D816V in combination with increase of VAF of additional mutations (RUNX1, #04; IDH2, #13; KRAS, #06) followed by disease progression and rapid death. Patient #04 progressed into sMCL and then sAML. (E) Acquisition of new mutations (JAK2 V617F, #11; NMP1, #15; KRAS/SETBP1, #03) with disease progression into ASM and associated polycythemia vera (ASM-PV, #11) or ASM-AML (#15) followed by death (#15, #03). Patient #11 with transfusion-dependent anemia at baseline became transfusion-independent. *, Clinical end points, including type of secondary neoplasm observed at the time of progression and death. dx, diagnosis.