Incidence of second primary malignancies and related mortality in imatinib-treated chronic myeloid leukemia patients

The majority of patients with chronic myeloid leukemia are successfully managed with life-long treatment with tyrosine-kinase inhibitors. In patients in chronic phase, other malignancies are among the most common causes of death, raising concerns on the relationship between these deaths and the off-target effects of tyrosine-kinase inhibitors. We analyzed the incidence of second primary malignancies, and related mortality, in 514 chronic myeloid leukemia patients enrolled in clinical trials with imatinib first-line. We then compared the observed incidence and mortality with those expected in the age- and sex-matched Italian general population, calculating standardized incidence and standardized mortality ratios. After a median follow-up of 74 months, 5.8% patients developed second primary malignancies. The median time from chronic myeloid leukemia to second primary malignancies diagnosis was 34 months. We did not find a higher incidence of second primary malignancies compared to the age- and sex-matched Italian general population, with standardized incidence ratios of 1.06 (95% C.I. 0.57-1.54) and 1.61 (95% C.I. 0.92-2.31) in males and females, respectively. Overall, 3.1% patients died for second primary malignancies. The death rate in patients with second primary malignancies was 53% (median overall survival: 18 months). Among females, the observed cancer-related mortality was superior to what expected in the age- and sex-matched Italian population, with standardized mortality ratio of 2.41 (95% C.I. 1.26 - 3.56). In conclusion, our analysis of imatinib-treated chronic myeloid leukemia patients did not disclose a higher incidence of second primary malignancies; however, second primary malignancies outcome was worse than expected. Clinicaltrials.gov: NCT00514488, NCT00510926.