Long-term outcome of patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors after imatinib failure is predicted by the in vitro sensitivity of BCR-ABL kinase domain mutations

Abstract

Secondary imatinib resistance in chronic myeloid leukemia (CML) is associated in approximately 50% of cases with mutations in the BCR-ABL kinase domain, necessitating switch to one of several new tyrosine kinase inhibitors (TKIs) that act differentially on mutated BCR-ABL. We assess here whether scoring mutation based on in vitro inhibitory concentration of each TKI-mutation pair can predict long-term clinical outcome. Among 169 patients with CML after imatinib failure, mutations were detected before TKI switch in 41 (48%) treated with dasatinib and 45 (52%) treated with nilotinib. Inhibitory concentration values for each TKImutation pair were stratified into high (n = 42), intermediate (n =..