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Imatinib efficacy in CML persists over time
The efficacy of imatinib for treatment of chronic myeloid leukemia persisted over time, according to nearly 11 years of follow-up from the open-label, multicenter IRIS trial.
Long-term administration did not appear associated with unacceptable cumulative or late toxic effects.
“This trial fundamentally changed CML treatment and led to marked improvements in prognosis for patients,” Andreas Hochhaus, MD, head of the department of hematology and medical oncology, as well as director of University Tumor Center at Jena University Hospital in Germany, and colleagues wrote.
Prior studies showed imatinib (Gleevec, Novartis) — a selective BCR-ABL1 kinase inhibitor — reduced annual age-adjusted mortality rates among patients with CML from 0.9 deaths per 100,000 persons in 1996 to 0.4 deaths per 100,000 persons in 2006.
The IRIS trial included 1,106 patients with newly diagnosed CML. Researchers randomly assigned patients to 400 mg oral imatinib per day (n = 553) or subcutaneous interferon alfa (5 million IU/m2 daily) plus 20 mg/m2 cytarabine daily for 10 days every month (n = 553).
Enrollment began in January 2000, and the last patient visit took place in January 2012.
Patients who did not achieved hematologic response by 6 months or major cytogenetic response by 1 year could cross over to the other regimen.
After 7 years, the trial was extended for imatinib therapy only. Patients who received interferon alfa plus cytarabine were eligible to continue in the trial if they crossed over to imatinib therapy.
EFS served as the initial primary endpoint. OS among patients who received imatinib served as the long-term primary endpoint.
Investigators used the Sokal Score — a scoring system based on age, spleen size, peripheral-blood platelet count and blast count — to determine patients’ overall prognosis.
Median follow-up was 10.9 years (range, 0-11.7).
About two-thirds (65.6%) of patients assigned interferon alfa plus cytarabine crossed over to imatinib (median time to crossover, 0.8 years). Therefore, newly published results focused on analyses of patients randomly assigned imatinib.
In the intention-to-treat population, 38 patients (6.3%) progressed to accelerated phase or blast crisis during study treatment. The estimated rate of freedom from progression to the accelerated phase or blast crisis at 10 years was 92.1% (95% CI, 89.6-94.5).
The estimated 10-year EFS rates were 79.6% (95% CI, 51.5-61.6) for patients assigned imatinib and 56.6% (95% CI, 51.5-61.6) for those assigned interferon alfa plus cytarabine. Estimated 10-year OS was 83.3% (95% CI, 80.1-86.6) among patients who received first-line imatinib.
Nearly half (48.3%) of patients assigned imatinib completed therapy; of this group, 82.8% experienced a complete cytogenetic response. Approximately 15% of patients discontinued treatment because of unsatisfactory effect or adverse events.
Fifty-one (9.3%) patients experienced serious adverse events. The most frequent event was abdominal pain, which was considered treatment-related in four patients. The frequency of these events decreased over time.
“The long-term results presented here highlight the clinical benefits observed in patients with CML over the past 15 years,” the researchers wrote.
Although imatinib controlled long-term disease, only a few patients would be considered cured, according to Dan L. Longo, MD, professor of medicine at Harvard Medical School, wrote in an accompanying editorial.
“We need to resist the temptation to be self-congratulatory,” Longo wrote. “The prognosis for patients with common cancers is improving somewhat, but none of the new tools appears to cure a majority of patients.
“We still need to learn how to combine therapies that have different targets, to identify patients who are likely to have a response, and to define mechanisms of resistance,” Longo added. “Although the journey to cancer cure has just begun, the use of imatinib to treat CML has pointed oncology in a new direction.” – by Melinda Stevens
Disclosures: Hochhaus reports advisory fees and travel support from Ariad, Bristol-Myers Squibb, Novartis and Pfizer; and grant support from Ariad, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures. HemOnc Today was unable to confirm Longo’s relevant financial disclosures at the time of reporting.