1. The efficacy of imatinib in chronic phase chronic myeloid leukemia (CML) persisted after 10-year follow-up.
2. No new significant adverse events related to imatinib treatment were found after long-term follow-up.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The 2003 IRIS trial (International Randomized study of Interferon and STI571) established imatinib as first-line treatment for CML. This trial initially compared imatinib with interferon alfa and cytarabine, with the majority of patients crossing over to the imatinib group due to superior safety and efficacy. This study reports the long-term safety and efficacy of the imatinib arm of the original trial after 10-year follow-up. The primary long-term outcome – overall survival – confirmed imatinib’s durability in chronic phase CML. Secondary outcomes included response rates, time to response, disease progression, safety, and drug-related adverse events. The majority of patients treated with imatinib had a complete cytogenetic response, while adverse events related to treatment remained uncommon. These results indicated that the efficacy of imatinib persisted over time without increased risk of adverse events.
This was a multicenter, open-label, parallel group, randomized, controlled trial that analyzed results from a large number of patients in chronic CML treated with imatinib. Limitations of the study included the large number of patients who had an unknown survival status, those without molecular or cytogenetic assessments, and the limited collection of long-term safety information. The trial could not demonstrate a survival advantage with imatinib treatment, since the majority of patients treated with interferon alfa and cytarabine crossed over to the imatinib arm.
In-Depth [randomized controlled trial]: This multicenter trial initially randomized 1106 patients to imatinib (n = 553) or interferon alfa and cytarabine (n = 553) from 2000 to 2012. The primary initial outcome was event-free survival (without progression to accelerated phase or blast crisis, loss of hematologic, or cytogenetic response). The primary long-term outcome was overall survival in the imatinib group only, due to cross over from the interferon alfa/cytarabine group. Secondary outcomes included response rates, time to response, disease progression, safety, and drug-related adverse events.
The median duration of follow-up was 10.9 years (range, 0 to 11.7) and the median duration of first-line imatinib therapy was 8.9 years (range, <0.1 to 11.7). The estimated overall survival rate at 10 years in the imatinib group was 83.3% (95% CI, 80.1 to 86.6). There was an 89.0% cumulative rate of major cytogenetic response and 82.8% complete cytogenetic response in the imatinib group at the end of the trial, with an estimated 49.1% complete response at 6 months. Among the 134 patients with cytogenetic assessment at 10 years, 123 (91.8%) had a complete cytogenetic response. Among the 204 patients who had molecular assessments that could be evaluated at 10 years,190 (93.1%) had a major response and 129 (63.2%) had a complete response. 51 of 551 patients (9.3%) receiving first-line imatinib had a serious adverse event, which was highest during the first year. No new safety signals were observed since the previous, 5-year analysis.
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