High rates of durable response are achieved with imatinib after treatment with interferon alpha plus cytarabine: results from the International Randomized Study of Interferon and STI571 (IRIS) trial.
BACKGROUND
Imatinib is the standard of care for newly diagnosed chronic-phase chronic myeloid leukemia. The largest randomized clinical trial of imatinib was the multinational IRIS trial in which 1106 patients were randomized to receive either imatinib 400 mg/day or a standard regimen of interferon-alpha plus cytarabine.


METHODS
Patients were allowed to cross over to the opposite treatment for intolerance, lack of response, disease progression, and, following release of the initial efficacy data, reluctance to remain on therapy with interferon-alpha plus cytarabine. The safety and efficacy of imatinib in patients who crossed over from interferon-alpha plus cytarabine to imatinib is reported here.


RESULTS
Of 553 patients originally assigned to interferon-alpha plus cytarabine, 65% crossed over to imatinib, of whom 67% continue to receive treatment. After a median of 54 months of imatinib treatment on study, 93% achieved complete hematologic remission, 86% achieved major cytogenetic remission, and 81% achieved a complete cytogenetic remission as the best observed response. Estimated rates of freedom from progression to accelerated or blast phase and overall survival were 91% and 89%, respectively, at 48 months after starting imatinib.


CONCLUSIONS
This is the largest analysis to date describing the efficacy of imatinib in patients who have received prior therapies for chronic myeloid leukemia and it demonstrates excellent responses to this treatment. (ClinicalTrials.gov identifier: NCT00006343).
Guilhot
François
F
Department of Oncology-Hematology and Cell Therapy, CIC 802 INSERM, CHU de Poitiers, Poitiers, France. f.guilhot@chu-poitiers.fr
Druker
Brian
B
Larson
Richard A
RA
Gathmann
Insa
I
So
Charlene
C
Waltzman
Roger
R
O'Brien
Stephen G
SG
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D018592:Cross-Over Studies; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D004487:Edema / Q000139:chemically induced; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality; D009120:Muscle Cramp / Q000139:chemically induced; D009325:Nausea / Q000139:chemically induced; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate