IRIS at Five Years Still Changing the Face of Long-term Chronic Myeloid Leukemia Therapy
IRIS at Five Years Still Changing the Face of Long-term Chronic Myeloid Leukemia Therapy
US Oncological Disease 2007 - Issue I
Published: October 2008
Published: October 2008
Although the level of cytogenetic response was predictive for long-term outcomes, statistically PFS and OS were not significantly different between 12-month CCyR and PCyR. Note that 64% of PCyR patients and 36% of patients without MCyR at 12 months subsequently achieved CCyR. Using the 18-month landmark, 50% of PCyR patients and 27% of patients without MCyR achieved CCyR at a later time.
Long-term outcomes were evaluated based on available bcr-abl transcript levels in patients with CCyR. A 3-log reduction from standardized baseline value in untreated patients was defined as a major molecular response (MMR). No patients who achieved both CCyR and MMR at 12 or 18 months progressed to accelerated phase or blast crisis by 60 months. Approximately 5% of patients with CCyR but no MMR at 12 months (p=0.007) and only 2% of CCyR patients without MMR at 18 months (p=0.11) subsequently progressed. Of approximately 25% of CCyR patients with available PCyR analysis who did not achieve MMR at 18 months, about half did achieve MMR at a later time and their estimated EFS rate at 60 months was 91%.
Owing to the a large number of patients in the IRIS trial who crossed over from imatinib to IFN-α + Ara-C, a retrospective analysis was performed comparing outcome of patients assigned to imatinib in the IRIS trial13 with patients assigned to the IFN-α + Ara-C arm included in the French multicenter trial (CML 91) before imatinib became available.14 Inclusion criteria of both studies were similar: patients with Ph+ chronicphase CML diagnosed within six months before randomization; hydroxyurea or anagrelide were allowed if needed. Patients who actually received the assigned study treatment were compared (n=551 for IRIS and n=325 for CML91). This comparison shows that for first-line therapy for newly diagnosed chronic-phase CML, imatinib is superior to prolonged therapy with IFN-α + Ara-C for rate of MCyR, CCyR, PFS, and overall survival. Nevertheless, patients who do not have access to or who cannot tolerate imatinib can have long PFS and overall survival with IFN-α + Ara-C therapy.
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