Front-line TKI therapy for chronic-phase CML: the luxury of choice.

The modern era of targeted tyrosine kinase inhibitor (TKI) therapy for the treatment of human malignancies was ushered in by the BCR-ABL TKI imatinib (Gleevec) in glorious fashion by Brian Druker and colleagues.[1] Upon its approval in 2001, imatinib was rapidly adopted (despite an absence of long-term outcome and safety data) as first-line therapy for newly diagnosed chronic myeloid leukemia (CML) patients in chronic phase—even for younger patients who were excellent candidates for the established curative procedure of allogeneic stem-cell transplantation. The enthusiasm for imatinib was largely based on its ease of administration, its good tolerability (particularly relative to interferon), and most notably, its efficacy. Complete cytogenetic response (CCyR), which had previously been recognized as a surrogate marker of progression-free and overall survival—and which remains a critical goal of treatment today—was achieved in the majority of patients treated with imatinib.[2] Longer-term follow-up has provided firm justification for the initial optimism regarding imatinib in cases of chronic phase CML. With 8 years of follow-up, it appears that the likelihood of dying of CML is approximately equivalent to the likelihood of dying of other causes,[3] and it is hoped that with longer follow-up and more access to effective next-generation TKIs, the majority of chronic-phase CML patients, in stark contrast to historical experience, will die of causes unrelated to CML or its treatment.