IRIS 6-year data confirm imatinib as standard CML Rx

February 1, 2008

Six-year results of the IRIS trial confirm imatinib (Gleevec) as the standard first-line therapy for chronic myelogenous leukemia

ATLANTA—Six-year results of the IRIS trial confirm imatinib (Gleevec) as the standard first-line therapy for chronic myelogenous leukemia, Andreas Hochhaus, MD, professor of internal medicine, the University of Heidelberg, Mannheim, Germany, said at ASH 2007 (abstract 25).

Overall survival at 6 years for patients receiving imatinib therapy was 88%. Dr. Hochhaus noted that if only CML-related deaths were taken into account, the estimated overall survival rate with imatinib was 95%.

"If this survival trend continues, many patients with CML may approach normal life expectancy with continued Gleevec treatment," said Brian Druker, MD, director of the of the Oregon Health & Science University Cancer Institute.

IRIS, launched in 2000, compared standard treatment with interferon-alfa plus cytarabine against imatinib in 1,106 patients with newly diagnosed Ph+ CML. Eventually, 66% of controls crossed over to imatinib, while only 2% on imatinib crossed over to interferon-alfa plus cytarabine. After 6 years, 181 patients had discontinued study treatment.

Event-free survival

At 6 years, event-free survival (EFS) for the imatinib patients was 83%, and progression-free survival—survival without CML progression to accelerated or blast phase—was 93%.

Dr. Hochhaus pointed out that annual event rates—ie, loss of complete hematologic or major cytogenetic response, progression, or death—have declined over the course of imatinib treatment, from a high of 7.5% in the second year of treatment to 0.8% in the 5th year and 0.4% in the 6th year.

Annual event rates for those achieving complete cytogenetic response (CCyR) declined from 5.4% in the 1st year to 0.3% in the 4th year, with no conversions to accelerated phase/blast crisis after the 3rd year.

Among patients with CCyR, 71% retained that status out to 6 years. Among those losing CCyR, 5% regained it and are still on imatinib. As of late January 2007, 63% (n = 349) of all imatinib-treated patients remained in CCyR.

Toxicity

Dr. Hochhaus noted that most grade 3-4 adverse events occurred early and declined in incidence with continued imatinib therapy. Importantly, he said, higher grade hematologic toxicity during years 1-2 was associated with worse EFS. Dr. Hochhaus commented that the lowered EFS may have been attributable to reduction of dose or discontinuation of imatinib therapy.

"The 88% overall survival with imatinib exceeds that of all other CML therapies," Dr. Hochhaus concluded. "Responses are durable, and the annual risk of progression decreases over time. Furthermore, there are no new safety findings with long-term follow-up."