Long-term Outcomes of tyrosine kinase inhibitors in chronic myeloid leukemia.

Long-term outcomes with tyrosine kinase inhibitors (TKI) show that their impact on CML is sustained as shown by 13 studies with 5- to 14-year-follow-up and numerous shorter-term studies of newly diagnosed chronic-phase CML. Twenty-five years of imatinib (IM)-treatment confirm its beneficial effect on survival and possibly cure of CML. Large randomized academic treatment optimization studies have confirmed and extended the pivotal International Randomized Study on Interferon and STI571 (IRIS). The 3 academic trials in Germany, France and the UK did not show benefit of the IM-interferon (IFN) combination, despite the immunomodulatory properties of IFN. Second generation (2G)-TKI induce responses faster than IM and recognize IM-resistance-mutations, but do not prolong survival compared to IM. Serious drug related reactions (ADR) limit the general use of 2GTKI despite frequent, but mostly mild IM-ADR. Molecular monitoring of treatment efficacy has been established serving as an example for other neoplasms. Comorbidities, transcript type and the negative impact of high-risk additional chromosomal abnormalities (ACA) were addressed. A new prognostic score (EUTOS-long-term-survival or ELTS-score) accounts for the fact that the majority of CML-patients die of other causes. Non-CML determinants of survival have been identified. Large and long-term observational studies demonstrate that progress with CML-management has also reached routine care in most, but not all instances. Despite merits of 2GTKI IM remains the preferred treatment option for CML due to its efficacy and superior safety.