Outcomes of chronic-phase chronic myeloid leukemia beyond first-line therapy

The therapeutic landscape of chronic-phase chronic myeloid leukemia (CP-CML) has truly been revolutionized with the advent of BCR-ABL1 tyrosine-kinase inhibitor (TKI) therapy. First-line therapy with the TKI imatinib has produced high rates of remissions among treatment-naive patients, as well as patients previously treated with interferon. However, imatinib resistance and intolerance remain significant clinical challenges. Dasatinib, nilotinib, bosutinib and ponatinib are more recently developed TKIs that have been shown to be very effective as second- or later-line treatment for CML after imatinib failure. Dasatinib and nilotinib are also approved for use in newly diagnosed patients with CP-CML, and produce faster responses when compared with first-line imatinib. Resistance or intolerance can occur with any of the currently available TKIs, necessitating a change to an alternative TKI or consideration of allogeneic hematopoietic stem cell transplant. Treatment options and outcomes for patients whose first-line therapy has failed are reviewed in depth in this article.