Maintaining treatment with imatinib as initial therapy in patients with chronic myeloid leukemia (CML) may yield positive outcomes, including increased overall survival to ≥5 years, according to a study published in the New England Journal of Medicine (NEJM). The follow-up study of the International Randomized Study of Interferon and ST1571 (IRIS), a multicenter, international, randomized, phase 3 trial, included patients aged 18 to 70 years diagnosed with Ph-positive CML in chronic phase within 6 months before the start of the study.
Maintaining treatment with imatinib as initial therapy in patients with chronic myeloid leukemia (CML) may yield positive outcomes, including increased overall survival to ≥5 years, according to a study published in the New England Journal of Medicine (NEJM).
In IRIS, researchers randomly assigned 553 participants to imatinib 400 mg once daily and 553 participants to interferon alfa 5 million U/m2 of body surface area plus cytarabine 20 mg/m2 of body surface area daily for 10-day cycles. Median follow-up was 60 months.
Patients taking imatinib who did not have a complete blood-related response within 3 months or whose bone marrow contained >65% Ph-positive cells at 12 months were allowed to receive increased doses of imatinib ≤400 mg twice daily, provided there were no dose-limiting side effects. Participants could switch to the other treatment group if, after 6 months of treatment, there was no complete blood-related response, there was no major cytogenetic response after 12 months, there was a relapse or increase in white-cell count, or patients were unable to tolerate treatment.
A total of 382 (69%) of the patients taking imatinib and 16 (3%) of the patients taking interferon alfa plus cytarabine continued their original treatment. Significantly, 359 patients (65%) assigned to interferon plus cytarabine switched to imatinib, but only 14 patients (3%) in the imatinib group crossed over to treatment with inter-feron alfa plus cytarabine. Commonly, patients cited intolerance of treatment (26%) as the reason they switched from interferon alfa to imatinib. Of those who discontinued treatment (n=178) in the interferon alfa plus cytarabine group, consent withdrawal (14%) and adverse events (6%) were the most common reasons for ending treatment. Among patients taking imatinib, 23 stopped treatment due to adverse events and 25 withdrew consent.
Complete cytogenetic response rates for patients taking imatinib were 69% at 12 months and 87% at 60 months. Approximately 7% of patients later developed accelerated-phase CML or blast crisis. Patients with a complete cytogenetic response or in whom levels of BCR-ABL transcripts had dropped by ≥3 log demonstrated a significantly lower risk of disease development compared with patients without a complete cytogenetic response (P<.001).
Approximate overall survival of patients taking imatinib as initial therapy was 89% at 5 years (95% CI, 86%–92%). This rate is higher than the rates observed in prior studies of CML treatment, the authors stated.
Common side effects associated with imatinib treatment included edema, including peripheral and periorbital edema (60%); nausea (50%); muscle cramping (49%); musculoskeletal pain (47%); diarrhea (45%); skin conditions (40%); fatigue (39%); abdominal pain (37%); headache (37%); and joint pain (31%). Grade 3 or 4 adverse events were minimized over time, and there was no clinically significant change in the side effect profile.
SOURCE Druker BJ, Guilhot F, O'Brien SG, et al; for the IRIS investigators. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–2417.