International Randomized Study of Interferon Vs STI571 (IRIS) 8-Year Follow up: Sustained Survival and Low Risk for Progression or Events in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Imatinib.

Abstract Abstract 1126 Poster Board I-148 Background The IRIS study demonstrated superior safety and efficacy of imatinib (IM) relative to interferon-αa + cytarabine. Based on results from this trial, IM is currently recommended as front-line therapy for CML-CP patients (pts). We report 8-yr follow-up of IRIS, evaluating long-term efficacy and safety of IM. Methods The 553 pts randomized to first-line IM were evaluated for cytogenetic and molecular responses, event-free survival (EFS), progression to accelerated-phase (AP) or blast crisis (BC), overall survival (OS), discontinuations, and frequency of serious adverse events (SAEs). EFS was defined as time until the first occurrence of any of the following: death from any cause, progression to AP/BC, loss of a complete hematologic response or major cytogenetic response, or an increasing white cell count to > 20 × 109/L. Yearly progression rates were calculated using the life-table method considering available follow-up. Following study drug discontinuation, pts were followed for OS and stem cell transplant (SCT) information. Results At the 8-yr data cut-off, 304 (55%) pts remained on IM study treatment, and 45% had discontinued treatment due to adverse events (AEs)/safety (6%), unsatisfactory therapeutic outcome (16%), SCT (3%), death (3%) or other reasons (17% for withdrawal or lack of renewal of consent and miscellaneous). No new safety issues were identified in a long-term analysis of serious adverse events. Estimated EFS at 8 yr was 81% and freedom from progression to AP/BC was 92%. Estimated OS was 85% at 8 yr, and 93% when only CML-related deaths and those prior to SCT were considered. Three events occurred in yr 8: 1 progression to AP/BC and 2 deaths unrelated to CML (chronic obstructive pulmonary disease 1; pneumonia aspiration 1). The annual rates of progression to AP/BC in yr 4 to 8 after initiation of therapy were 0.9%, 0.5%, 0%, 0%, > 0–35% Ph+ metaphases) at 6 Bristol-Myers Squibb: Consultancy; Calistoga: Research Funding; Genzyme: Research Funding. O'Brien:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Wyeth: Research Funding. Guilhot:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria. Goldman:Novartis: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau. Hochhaus:Novartis: Research Funding. Hughes:Bristol-Myers Squibb: Advisor, Honoraria, Research Funding; Novartis: Advisor, Honoraria, Research Funding. Radich:Novartis: Consultancy, Honoraria, Research Funding. Hatfield:Novartis: Employment, Equity Ownership, Patents MolecularMD: Equity Ownership; Roche: Consultancy; Cylene Pharmaceuticals: Consultancy; Calistoga Pharmaceuticals: Consultancy; Avalon Pharmaceuticals: Consultancy; Ambit Biosciences: Consultancy; Millipore via Dana-Farber Cancer Institute: Patents Novartis, ARIAD, Bristol-Myers Squibb: Research Funding.