Imatinib Long-Term Effects Study: Global Independent Assessment of Imatinib in Chronic Myeloid Leukemia: Results At 8 Years,

Abstract 3766

The independent, multicenter Imatinib Long Term Effects (ILTE) study assessed overall survival, loss of complete cytogenetic remission (CCyR), attainment of negative Philadelphia chromosome hematopoiesis assessed with quantitative polymerase chain reaction (PCR), serious adverse events (SAE), and toxicities not qualifying as SAE (NSAE) but judged by treating physicians as substantially affecting quality of life. The ILTE study also investigated the development of second tumours after at least two years of treatment. Consecutive CML patients, who started imatinib before 2005 and who were in CCyR after two years, were eligible. Overall survival, incidence of the first adverse events, and loss of CCyR were estimated according to the Kaplan-Meier method and compared with the standard log-rank test. Cumulative incidence of death was broken down into incidence related or unrelated to CML, accounting for competing risks. Standardized incidence ratio were calculated based on population rates specific for gender and age classes.

The results at December 31st 2008 were published in J Natl Cancer Inst 2011; 103: 553–561. Here we report the results updated at December 31st, 2009, where a total of 832 patients were enrolled with a median treatment duration of 6.7 years. A comparison of the observed mortality rate in CML patients with the rate in the general Italian population showed no excess mortality. Thirty-three deaths were observed (8 CML-related), with a mortality incidence rate of 0.8 per 100 person-years (standardized incidence ratio = 0.85; 95% CI = 0.58 to 1.19). Similar results were obtained when this analysis was restricted to Italian patients. The CML-related death rate was 0.12 per 100 person-years. There were 139 recorded SAE, of which 19.4% were probably related to imatinib. Among the 830 NSAEs (which developed in 57.8% of patients and were possibly related to imatinib in 68.2% of the 830 events), the most frequent ones were muscle cramps, asthenia (observed in 4.9% of patients), edema, skin fragility, diarrhea, conjunctival hemorrhages, osteoarticular pain and tendon or ligament lesions. Nineteen patients (2.3%) discontinued imatinib because of drug-related toxicities. Fifty-three patients lost CCyR, corresponding to a rate of 1.4 per 100 person years (1.1% in patients who received imatinib as first line treatment). Durable (greater than 1 year) Philadelphia negative hematopoiesis, as evaluated by PCR was attained by 125 patients (15%).

The onset of second tumours was also evaluated: 34 patients developed second cancers. The overall rate was not significantly different from that of the general population (SIR = 0.9, 95% CI = 0.63 to 1.26), with the exception of prostate cancer (SIR = 2.86; 95% CI = 1.48 to 4.99).

In conclusion, CML-related deaths are uncommon in CML patients who are in CCyR two years after starting imatinib. Survival is not statistically significantly different from that of the general population. Side effects are present but generally not serious. A higher incidence of prostate cancer, to be confirmed and further analyzed, was observed.