The Cure of Chronic Myeloid Leukemia: Are We There Yet?

PURPOSE OF REVIEW: A large number of chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitors (TKIs) can now enjoy a deep molecular control of the disease and the life span could be approaching that of normal population. The purpose of the review is to evaluate current evidence and if we can talk of a cure. RECENT FINDINGS: The revolution in the treatment of CML was apparent since the exquisite efficacy of imatinib mesylate, a tyrosine kinase inhibitor, was proven and received approval for newly diagnosed cases in 2001. Subsequent development of second-generation TKIs, nilotinib and dasatinib, has increased our armamentarium. These TKIs, because of their safety and efficacy, are now offered as first-line therapy, thus relegating use of allogeneic transplant to the second line or beyond. It has also been possible to stop TKIs in selected subsets in whom leukemia burden became undetectable and ~ 40% of them remain drug-free for a number of years-treatment-free remission (TFR). Nevertheless, much work needs to be done to eradicate leukemia stem cells as current TKIs appear unable to eradicate leukemia stem cells (LSC). Effective treatment of more advanced phase CML remains elusive. Further efforts to develop newer molecules targeting BCR-ABL and beyond must be continued. Although TKIs have revolutionized treatment of chronic phase CML, longer follow-up is necessary to realize their curative potential. Equally important is to explore newer targets and development of more potent small molecules for eradication of leukemia clone in all patients.