Efficacy and safety of imatinib in patients with chronic myeloid leukemia and complete or near-complete cytogenetic response to interferon-alpha.
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-alpha (n = 7 patients) maintained an MMR while receiving imatinib. No patients discontinued imatinib due to toxicity, but 1 patient withdrew consent.


CONCLUSIONS
These data suggest that switching IFN-alpha-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.
Branford
Susan
S
Division of Molecular Pathology, Institute of Medical and Veterinary Science, Adelaide, SA, Australia. susan.branford@imvs.sa.gov.au
Hughes
Timothy
T
Milner
Alvin
A
Koelmeyer
Rachel
R
Schwarer
Anthony
A
Arthur
Chris
C
Filshie
Robin
R
Moreton
Susan
S
Lynch
Kevin
K
Taylor
Kerry
K
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D003967:Diarrhea / Q000139:chemically induced; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D010352:Patient Dropouts; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D016896:Treatment Outcome
D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl