SIDEBAR: Maximizing Tyrosine Kinase Inhibitor Therapy in CML

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Second-generation tyrosine kinase inhibitors as initial therapy in chronic myeloid leukemia (CML) continue to prove their worth by demonstrating protection against disease progression and by producing increasingly “higher quality” remissions, said Attaya Suvannasankha, MD, of Indiana University School of Medicine, Indianapolis, at the Best of ASCO Boston meeting. “But the translation of this benefit—survival, ‘curative’ potential—is yet to be determined,” she added.

Discussing the clinical implications of recent data, she sees the use of a second-generation tyrosine kinase inhibitor in the front-line setting “worthwhile,” as it is associated with “greater benefit, higher efficacy, and deeper responses” than imatinib and is essentially even more effective in patients with the T315I mutation. At this point, however, Dr. Suvannasankha still typically initiates treatment with imatinib. “We have long-term follow-up with imatinib, and it is well tolerated in most patients,” she explained.

Alternative Strategy

Dr. Suvannasankha emphasized that her threshold for switching to a second-generation tyrosine kinase inhibitor is low, and when patients do not achieve a major molecular response by 3 months or, at the most, 6 months, or when they do not tolerate imatinib well, she starts them on nilotinib or dasatinib (selecting the agent according to toxicity profile). She does not advocate increasing the imatinib dose. “Switching to a second-generation tyrosine kinase inhibitor is an effective, alternative way to improve the quality of molecular remissions,” she said.

She acknowledged, however, that front-line use of second-generation tyrosine kinase inhibitors is rational, but gains in progression-free and overall survival are not yet apparent, “and progression and deaths still occur.” Nevertheless, comparisons with imatinib consistently show the advantages of these agents in terms of depth of response, likelihood of response, and reduction in transformation rates. “The manifestation of these benefits may take more time,” she said.

Looking ahead, Dr. Suvannasankha commented that ponatinib provides a “remarkable ability to salvage resistant disease, especially T315I patients, and its earlier use may prove even better, as was seen in the less treated T315I cohort in the trial.” ■

Disclosure: Dr. Suvannasankha reported no potential conflicts of interest.

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