March 22, 2010 — Patients with chronic myelogenous leukemia (CML) who are taking imatinib (Gleevec) can expect to live as long as the general population, according to results from a new study published online March 21 in the Journal of the National Cancer Institute.
Patients in complete cytogenetic remission (CCyR) after 2 years have a survival rate that is comparable to the population at large; this is in contrast to survival after other therapies such as bone marrow transplantation.
The results of this study are an "indication of how profoundly imatinib has changed the clinical course of CML," the authors write. "These data may help physicians to advise CML patients about their prognosis on imatinib."
Few Deaths From CML
The multicenter Imatinib Long-Term Side Effects (ILTE) study enrolled 832 patients who were treated for a median of 5.8 years and who were in CCyR after approximately 2 years of imatinib treatment. Within the follow-up period, 20 deaths occurred, for a mortality rate of 4.8%. This rate was similar to what would be expected in a comparable cohort in the general population.
Only 6 of these deaths were attributable to CML progression. The authors point out that approximately 6 years after beginning treatment with imatinib, almost 95% of patients maintained CCyR. At 8 years, CML-related mortality accounted for only 1% of patients.
A Cure on the Horizon?
Because the ILTE is an independent, nonindustry-sponsored trial, it adds "real-life long-term" data on the tolerability and efficacy of imatinib in CML, writes B. Douglas Smith, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, in an accompanying editorial.
He also notes that even though the authors did not address this issue in their paper, one of the most important contributions of the ILTE report is that it might "help us with our focus on curing patients with CML."
The tyrosine kinase inhibitors "are profoundly effective drugs that induce durable responses in the majority of CML patients and do so in a tolerable manner," Dr. Smith writes. "And these agents create a platform from which we can entertain the possibility of curing CML patients outside of the setting of allogeneic stem cell transplantation."
"It is now time for clinical and laboratory investigators to build on this platform and work to turn good and great responses into cures," he adds.
Long Lasting Effect
It has been well established that imatinib slows the development of CML, but the available data on morbidity and mortality largely stem from industry-sponsored trials that were conducted in selected research-intensive institutions. Information from independent long-term field studies has been lacking.
In this study, Carlo Gambacorti-Passerini, MD, from the University of Milano Bicocca/San Gerardo Hospital in Monza, Italy, and colleagues sought to evaluate the long-term effects of imatinib in CML in an independent multicenter trial.
The study was conducted in 27 centers in Europe, North and South America, Africa, the Middle East, and Asia. The median follow-up was 3.8 years (range, 0.5 to 7.1 years), or 5.8 years (range, 2.5 to 9.1 years) from the beginning of imatinib treatment. A total of 3247 person-years were available for analysis.
The median duration of treatment was longer for patients who received imatinib as second-line therapy than for those who received it as first-line treatment (6.3 vs 4.9 years). The median dose of imatinib was 400 mg/day at all years of follow-up, and the median time to CCyR after starting imatinib was 6.5 months.
At 6 years, the vast majority (94.9%) maintained their CCyR, which declined only moderately at 8 years (89.5%; 95% confidence interval [CI], 85.4% to 93.8%). A total of 45 patients lost CCyR during the observation period, which corresponds to an overall rate of 1.4 per 100 person-years.
In the cohort that began imatinib as first-line treatment, 15 lost CCyR, corresponding to a rate of 1.3 per 100 person-years (95% CI, 0.8 to 2.2), compared with 1.5 per 100 person-years (95% CI, 1.0 to 2.1) in patients that began imatinib as second-line therapy. The median time to loss of CCyR was 2.6 years, which corresponds to 4.6 years of treatment.
The authors note that deaths attributed to CML were uncommon in patients who were in CCyR for 2 years after beginning imatinib treatment; these patients had a mortality rate that was comparable to the general Italian population. Patients in this population are more likely to die of causes unrelated to CML, they write.
Among patients who received imatinib as first-line therapy, the annual rate of CCyR loss was 0.6 (95% CI, 0.1 to 2.2) in the third year of imatinib treatment, 1.5 (95% CI, 0.6 to 3.5) in the fourth year, and 2.6 (95% CI, 1.1 to 5.6) in the fifth year. In the sixth year, no one in the cohort had a loss of CCyR.
However, the authors emphasize that it is "important to remember that patients entered the ILTE study only if they were in CCyR after 24 months of imatinib treatment."
Adverse Events
Overall, long-term toxicity was modest, and imatinib was discontinued in 75 patients (9.0%) because of adverse effects. A total of 139 serious adverse events were reported, but only 27 of them (19.4% in 3.2% of patients) were considered to be possibly linked to imatinib.
These serious adverse events were reported in 7 patients with gastrointestinal toxicity (diarrhea, esophagitis, gastritis, pancreatitis, and liver toxicity), 5 with cardiovascular events (angina, heart failure, and myocardial infarction), 3 with tendon or ligament lesions, 4 with infections, 2 with fever, and 1 with skin rash.
The study was funded by the Italian Drug Safety Agency, the Italian Association for Cancer Research, and the Lombardy Regional Government.
J Natl Cancer Inst. Published online March 21, 2011. Abstract, Abstract
Patients in complete cytogenetic remission (CCyR) after 2 years have a survival rate that is comparable to the population at large; this is in contrast to survival after other therapies such as bone marrow transplantation.
The results of this study are an "indication of how profoundly imatinib has changed the clinical course of CML," the authors write. "These data may help physicians to advise CML patients about their prognosis on imatinib."
Few Deaths From CML
The multicenter Imatinib Long-Term Side Effects (ILTE) study enrolled 832 patients who were treated for a median of 5.8 years and who were in CCyR after approximately 2 years of imatinib treatment. Within the follow-up period, 20 deaths occurred, for a mortality rate of 4.8%. This rate was similar to what would be expected in a comparable cohort in the general population.
Only 6 of these deaths were attributable to CML progression. The authors point out that approximately 6 years after beginning treatment with imatinib, almost 95% of patients maintained CCyR. At 8 years, CML-related mortality accounted for only 1% of patients.
A Cure on the Horizon?
Because the ILTE is an independent, nonindustry-sponsored trial, it adds "real-life long-term" data on the tolerability and efficacy of imatinib in CML, writes B. Douglas Smith, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, in an accompanying editorial.
He also notes that even though the authors did not address this issue in their paper, one of the most important contributions of the ILTE report is that it might "help us with our focus on curing patients with CML."
The tyrosine kinase inhibitors "are profoundly effective drugs that induce durable responses in the majority of CML patients and do so in a tolerable manner," Dr. Smith writes. "And these agents create a platform from which we can entertain the possibility of curing CML patients outside of the setting of allogeneic stem cell transplantation."
"It is now time for clinical and laboratory investigators to build on this platform and work to turn good and great responses into cures," he adds.
Long Lasting Effect
It has been well established that imatinib slows the development of CML, but the available data on morbidity and mortality largely stem from industry-sponsored trials that were conducted in selected research-intensive institutions. Information from independent long-term field studies has been lacking.
In this study, Carlo Gambacorti-Passerini, MD, from the University of Milano Bicocca/San Gerardo Hospital in Monza, Italy, and colleagues sought to evaluate the long-term effects of imatinib in CML in an independent multicenter trial.
The study was conducted in 27 centers in Europe, North and South America, Africa, the Middle East, and Asia. The median follow-up was 3.8 years (range, 0.5 to 7.1 years), or 5.8 years (range, 2.5 to 9.1 years) from the beginning of imatinib treatment. A total of 3247 person-years were available for analysis.
The median duration of treatment was longer for patients who received imatinib as second-line therapy than for those who received it as first-line treatment (6.3 vs 4.9 years). The median dose of imatinib was 400 mg/day at all years of follow-up, and the median time to CCyR after starting imatinib was 6.5 months.
At 6 years, the vast majority (94.9%) maintained their CCyR, which declined only moderately at 8 years (89.5%; 95% confidence interval [CI], 85.4% to 93.8%). A total of 45 patients lost CCyR during the observation period, which corresponds to an overall rate of 1.4 per 100 person-years.
In the cohort that began imatinib as first-line treatment, 15 lost CCyR, corresponding to a rate of 1.3 per 100 person-years (95% CI, 0.8 to 2.2), compared with 1.5 per 100 person-years (95% CI, 1.0 to 2.1) in patients that began imatinib as second-line therapy. The median time to loss of CCyR was 2.6 years, which corresponds to 4.6 years of treatment.
The authors note that deaths attributed to CML were uncommon in patients who were in CCyR for 2 years after beginning imatinib treatment; these patients had a mortality rate that was comparable to the general Italian population. Patients in this population are more likely to die of causes unrelated to CML, they write.
Among patients who received imatinib as first-line therapy, the annual rate of CCyR loss was 0.6 (95% CI, 0.1 to 2.2) in the third year of imatinib treatment, 1.5 (95% CI, 0.6 to 3.5) in the fourth year, and 2.6 (95% CI, 1.1 to 5.6) in the fifth year. In the sixth year, no one in the cohort had a loss of CCyR.
However, the authors emphasize that it is "important to remember that patients entered the ILTE study only if they were in CCyR after 24 months of imatinib treatment."
Adverse Events
Overall, long-term toxicity was modest, and imatinib was discontinued in 75 patients (9.0%) because of adverse effects. A total of 139 serious adverse events were reported, but only 27 of them (19.4% in 3.2% of patients) were considered to be possibly linked to imatinib.
These serious adverse events were reported in 7 patients with gastrointestinal toxicity (diarrhea, esophagitis, gastritis, pancreatitis, and liver toxicity), 5 with cardiovascular events (angina, heart failure, and myocardial infarction), 3 with tendon or ligament lesions, 4 with infections, 2 with fever, and 1 with skin rash.
The study was funded by the Italian Drug Safety Agency, the Italian Association for Cancer Research, and the Lombardy Regional Government.
J Natl Cancer Inst. Published online March 21, 2011. Abstract, Abstract
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