Benefits of Imatinib in Patients With Chronic Myeloid Leukaemia Extend to 8 Years: Presented at ASH
By Betty S. Riggs
NEW ORLEANS, LA -- December 6, 2009 -- Patients with chronic myeloid leukaemia in the chronic phase (CML-CP) who respond to imatinib treatment have a low risk of progression to accelerated phase (AP) or blast phase (BP) during 8 years of follow-up, according to results of a study presented here at the American Society of Hematology (ASH) 51st Annual Meeting and Exposition.
Michael Deininger, MD, PhD, Oregon Health & Science University, Portland, Oregon, reported the findings on December 5.
In the International Randomized Study of Interferon vs STI571 (IRIS) trial, previously untreated adults with Philadelphia+ (Ph+) CML-CP were randomised to imatinib 400 mg daily (n = 553) or interferon alfa at 5 million IU/m2 plus cytarabine 20 mg/m2 (IFN-ara-C; n = 553).
In this 8-year follow-up study, patients randomised to first-line imatinib were evaluated for cytogenetic and major molecular responses, event-free survival (EFS), progression to AP or BC, and overall survival (OS). EFS was defined as time until the first occurrence of any of the following: death, progression to AP/BC, loss of a complete haematological response (CHR) or major cytogenetic response (MCyR), or an increasing white cell count to >20 x 109/L. At the 8-year data cut-off, 55% (n = 304) patients remained on first-line imatinib.
EFS at 8 years was 81%, and freedom from progression to AP/BC was 92%. Three events occurred in year 8: 1 progression to AP/BC and 2 deaths unrelated to CML. Estimated OS was 85% at 8 years, and 93% when only CML-related deaths were considered.
The best observed rate of complete CyR was 83% (457/553); though, 82 imatinib-treated patients had documented loss of complete CyR during treatment, 15 progressing to AP/BC.
Achieving minor CyR (>35%–65% Ph+ metaphases) at 3 months, partial CyR (>0%–35% Ph+ metaphases) at 6 and 12 months, and complete CyR at 18 months were prognostic indicators of stable complete CyR and lack of events. According to Dr. Deininger, the study demonstrates that clinicians should determine cytogenetic response periodically during long-term treatment since this provides prognostic information.
No new safety issues were identified in a long-term analysis of serious adverse events (SAEs). Since year 5, 9 patients (2.3%) had the following SAEs with a suspected relationship to imatinib: cardiac event (3), vomiting (1), chest pain (1), inclusion body myositis (1), colon cancer (1), squamous cell carcinoma (1), multiple sclerosis (1), dyspnoea (1), and polymorphic light eruption (1).
Reasons for treatment discontinuation (45%) included the following: AEs/abnormal laboratory values (5.4%), unsatisfactory therapeutic outcome (13.9%), stem cell transplantation (2.9%), death (2.9%), withdrawal of consent (8.0%), no re-consent to protocol amendment (3.4%), crossed over to IFN +ara-C (2.5%), or other reasons (6%).
After 8 years of follow-up, the IRIS study continues to show the long-term safety and efficacy of IM.
This study was supported by Novartis Pharmaceuticals Corporation and Novartis Pharma AG.
[Abstract title: 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 1126]
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