Navigating the road toward optimal initial therapy for chronic myeloid leukemia.
OBJECTIVE
Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML) and are now widely accepted as the initial therapy of choice in this disease, supplanting interferon and allogeneic stem cell transplantation. There are currently three drugs approved by the US Food and Drug Administration (FDA) for front-line treatment of CML: imatinib, nilotinib, and dasatinib. A fourth drug, bosutinib, may also win FDA approval in 2011. The goal of this review is to summarize the most recent information on initial treatment of CML and to aid clinicians in managing newly diagnosed CML patients.


RESULTS
Phase III studies comparing imatinib with nilotinib or dasatinib in newly diagnosed CML were published in June 2010, leading to accelerated FDA approval for both of these 'second-generation' TKIs for initial therapy of CML. There are significant differences between the agents in terms of frequency and rate of responses, progression-free survival, and side-effects. However, the follow-up period on these trials is short, and there are as yet no significant differences in overall survival. Guidelines for monitoring CML patients on TKI therapy have been recently revised.


CONCLUSIONS
Management of newly diagnosed CML patients in the coming decade will begin to resemble antibiotic treatment of infection, with therapy individualized based on patient risk factors, co-morbidities, and tolerability. In addition, the cost of therapy will emerge as an important consideration as generic imatinib becomes available in 2015. In this context, clinical trials to guide decision-making in newly diagnosed CML patients are needed.
Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts 02111, USA.
Ross A
RA
Okimoto
Richard A
RA
Van Etten
D000814:Aniline Compounds / Q000627:therapeutic use; D001549:Benzamides; D002986:Clinical Trials as Topic; D000069439:Dasatinib; D018572:Disease-Free Survival; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D009570:Nitriles / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use
D000814:Aniline Compounds; D001549:Benzamides; D009570:Nitriles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011804:Quinolines; D013844:Thiazoles; C471992:bosutinib; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib
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