Incidence of second malignancies during treatment of chronic myeloid leukemia with tyrosine kinase inhibitors in the Czech Republic and Slovakia

Abstract

Tyrosine kinase inhibitors (TKI) have completely changed the prognosis of patients with Ph+ chronic myeloid leukemia (CML). The occurrence of a second malignancy (SM) in CML patients successfully treated with TKI may significantly affect their prognosis. In a retrospective study of 1,038 patients with CML treated at 10 centers in the Czech Republic and Slovakia between 2000 and 2009, SM was detected in 35 (3.37%) patients after TKI therapy was initiated. The median intervals from the diagnosis of CML and from the start of TKI therapy to the diagnosis of SM were 58 months (range 2 - 214) and 32 months (range 1 - 102), respectively. The observed age-standardized incidence of SM after the start of TKI therapy was 8.95 / 1,000 person-years. Comparison of the incidence of SM in CML patients with population data was performed only for patients from the Czech Republic. The age-standardized incidence rate of all malignant tumors except non-melanoma skin cancers was 6.76 (95% CI: 6.74; 6.78) / 1,000 person-years in 2000 - 2007 while the incidence rate of SM in 708 CML patients from the Czech Republic treated with TKI was 9.84 (95% CI: 6.20; 13.48) / 1,000 person-years, i.e. 1.5-fold higher, although the difference was statistically insignificant. The distribution of SM types in CML patients treated with TKI was similar to that in the age-standardized general Czech population. The median overall survival (OS) of patients treated with TKI who also developed SM (57 months) was shorter than the OS of patients treated with TKI but not suffering from SM (median OS not reached, log rank test p < 0.001. Prospective long-term population-based studies in CML patients treated with TKI as first-line therapy are needed to determine the relationship of SM to KTI therapy.