Abstract
Promyelocytic blast crisis (BC) of CML is an extremely rare event, with only seven cases described as arising during therapy with TKIs. We present a 68-year-old male who developed promyelocytic blast crisis 12 months after CML diagnosis and start of Imatinib therapy, confirmed by the concomitant presence of the t(15;17) and t(9;22) translocations in the leukemic cells. Molecular remission for the PML-RARA clone was achieved with standard acute promyelocytic leukemia induction therapy with ATRA and idarubicin. However, BCR-ABL showed resistance to first-line Dasatinib and second-line Ponatinib, principally due to the presence of multiple mutations in ABL1 kinase domain, including T315I. Hematological and molecular response was achieved with Asciminib, a first‐in‐class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor in combination with pulsed ATRA as post-remission strategy. Of the 7 cases of promyelocytic BC reported in the era of TKI therapy for CML, this is the first case effectively treated with Asciminib therapy.