Efficacy and safety of imatinib in patients with chronic myeloid leukemia and complete or near-complete cytogenetic response to interferon-α

BACKGROUND. interferon-alpha (IFN-alpha) confers a survival advantage for the minority of patients with chronic myeloid leukemia (CML) who achieve a complete cytogenetic response. The question of whether IFN-alpha-responsive patients can experience further improvements with imatinib has not been answered. Imatinib offers clear quality of life advantages. Furthermore, patients who achieve a major molecular response (MMR) while receiving imatinib are likely to remain progression free. METHODS. A total of 23 patients treated for a median of 4.5 years with IFN-alpha (range, 1.6-14.3 years) who had achieved a complete (Philadelphia chromosome [Ph] negative, n = 15 patients) or near-complete (1-10% Ph, n = 8 patients) cytogenetic response were studied. The primary objective was to determine whether ceasing therapy with IFN-alpha and switching to 12 months of imatinib treatment at a dose of 400 mg/day could improve the molecular response as assessed by real-time quantitative polymerase chain reaction of BCR-ABL transcript levels. Safety was also assessed. RESULTS. Every patient who had not achieved an MMR while receiving IFN-alpha (n = 16 patients) achieved an MMR after a median of 3 months of imatinib treatment. Significant BCR-ABL reductions (median, 63-fold; range, 18-425-fold) occurred in 15 of these patients. Every patient who had already achieved an MMR while receiving IFN-a (n = 7 patients) maintained an MMR while receiving imatinib. No patients discontinued imatinib due to toxicity, but I patient withdrew consent. CONCLUSIONS. These data Suggest that switching IFN-a-responsive patients to imatinib leads to a rapid improvement in achieving an MMR, a response with established prognostic value, and is well tolerated. The study should help patients and their physicians make evidence-based decisions regarding the potential benefits and risks of switching to imatinib.