Secondary malignancies after chronic myeloid leukaemia upon TKI treatment: Population trends and outcomes

The life expectancy of most chronic myeloid leukaemia (CML) patients is nearly comparable to that of the general population owing to the application of tyrosine kinase inhibitors (TKIs). Hence, focus has shifted towards long-term adverse effects, especially the emergence of secondary malignancies. A retrospective study from 11 institutions was performed in 139 CML patients with secondary malignancies. The median ages at diagnosis of CML and secondary malignancy were 51 years (range, 13-88 years) and 53 years (range, 18-91 years). After a median follow-up of 85 months, the median time from diagnosis of CML to secondary malignancy was 48 months (range, 1-264 months). The use of two or more TKIs was a significant risk factor for the latency period of secondary malignancies (odds risk [OR] of 4.281, 95% confidence interval [CI] 1.369-13.390, p = 0.012). Male sex was an independent risk factor associated with worse overall survival (hazard ratio [HR] of 0.329, 95% CI 0.138-0.779, p = 0.012) and event-free survival (HR of 3.640, 95% CI 1.485-8.925, p = 0.005). Endocrine neoplasm was the most common subtype (28.8%, 40/139). Gastrointestinal, genitourinary and cutaneous malignancies demonstrated a male predominance. Then, male sex was associated with inferior outcomes in CML patients with secondary malignancies, and prospective studies are warranted to elucidate the underlying biological mechanisms.