Even Better Kinase Inhibitors for Chronic Myeloid Leukemia

Published - Written by Karen Buckley

Imatinib, a BCR-ABL kinase inhibitor, has been a major advance in first-line treatment for patients with chronic myeloid leukemia (CML), and has been established as the standard of care for this disease.  Dasatinib and nilotinib are two next-generation kinase inhibitors that have been used effectively as second-line treatment for certain patients.  This week, results being presented at the American Society of Clinical Oncology Annual Meeting and simultaneously published in NEJM demonstrate in two different up-front comparisons that using either dasatinib or nilotinib as first-line treatment produces a more complete response, and does so faster than imatinib.

In a randomized, open-label study, Saglio et al. assigned 846 patients to receive nilotinib at 300 mg twice daily, nilotinib at 400 mg twice daily, or imatinib at 400 mg once daily.  At 12 months, the rates of major molecular response for either dose of nilotinib were nearly twice that for imatinib.

Kantarjian et al. randomly assigned 519 patients to receive 100 mg of dasatinib daily or 400 mg of imatinib daily.  Dasatinib induced significantly higher and faster rates of complete cytogenetic response and major molecular response.

“Both drugs were shown to produce a faster, deeper, more complete molecular response,” says NEJM deputy editor, Dan Longo. “These results broaden the choice for physicians and patients with CML.”

In an accompanying editorial, Charles L. Sawyers, M.D. of Memorial Sloan-Kettering Cancer Center notes, “All three drugs have outstanding safety profiles, but there are modest differences in side effects that might lead patients to switch from one drug to another…Ironically, imatinib may survive the challenge on the basis of economic rather than scientific factors, since it could be available in generic form as early as 2014. With rising pressure to balance cost and efficacy, patients and payers may be forced to select the cheapest among three excellent treatment options.”

How will this change your recommendations for newly-diagnosed CML patients?  Will you consider either of these drugs as front-line therapy over the standard care of imatinib?