New data from the largest study of CML patients (1106 patients included) ever conducted International Randomized IFN vs. ST1571 (IRIS) study, were presented today at the annual meeting of the American Society of Hematology (ASH). In the study, newly diagnosed patients with chronic-phase Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) who achieved cytogenetic responses early had improved rates of progression-free survival compared to those who did not achieve early responses. Responses to imatinib were shown to be durable at 42 months.
"The IRIS study continues to show durable responses in patients treated with imatinib," said Pr Francois Guilhot, Head of Oncology Hematology and Cell Therapy Department, CHU La Miletrie, Poitiers, France. "For patients who achieved the highest responses at 12 months, the probability of remaining free of the leukaemia was very high."
Study Details
The landmark analysis showed that at 42 months, 84% of patients taking imatinib remained progression free, and only 6% progressed to the more advanced disease stages (accelerated phase and blast crisis). Overall survival (based on CML-related deaths) in patients treated with imatinib was 97% at 42 months. Patients taking imatinib as first treatment who achieved a complete cytogenetic response (CcyR) within 12 months of therapy had a 93% progression free survival rate at 42 months, compared with 74% in those without CcyR.
For patients who had achieved CcyR and a thousand-fold (3 log) or greater reduction in Bcr/Abl transcript level (called a molecular response) at 12 months, the probability of remaining progression free was 98% at 42 months, compared with 90% for patients with CcyR and less than a thousand-fold reduction and 75% for patients who had not achieved CcyR.
In CML, a molecular response is the disappearance or reduction in quantities of Bcr-Abl transcripts, which produce the abnormal protein responsible for driving the proliferation of white blood cells that occurs in CML patients. CHR refers to the normalization of blood counts, lasting for at least four weeks; however, the Ph chromosome positive (Ph+) cells may still be present. In McyR, less than 35% of cells containing the Philadelphia chromosome (the genetic abnormality that characterizes most cases of CML) are detected. In CcyR, Ph+ cells remain.
This study, abstract n°21, was published in Blood, Volume 104, Issue 11, November 16, 2004
About IRIS Study
IRIS: the largest Phase III CML study to date.
From June 2000 to January 2001, 1106 patients were enrolled at 117 centers in 16 countries in the IRIS study (553 randomized to each treatment arm). This was the largest and most rapidly accrued phase III CML to date
The IRIS study (study 106) protocol allows for a crossover in the case of lack of response, loss of response, or intolerance of treatment.
After interim analysis of the trial data, the initial study protocol was amended by the Independent Data Monitoring Board (IDMB) to enable patients in either arm to cross over if no MCR had occurred after 1 year of treatment, instead of 2 years as initially required, and to enable patients in the IFN + ara-C arm to cross over to imatinib at any time, if desired.