Deep molecular response (MR4.5) as a target of therapy with tyrosine kinase inhibitors. MR4.5 – goal of CML treatment Review article
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Abstract
Chronic myeloid leukemia (CML) accounts for 15% of diagnosed leukemias. The annual incidence in two Polish regions has been calculated for 0.7/100,000 of general population. Introduction of tyrosine kinase inhibitors (TKIs) have substantially improved not only the prognosis of CML, but also changed the treatment goals, and the expectations of patients and physicians. The goals of CML therapy include: to prevent the progression towards accelerated phase and blastic phase, to eliminate the risk of death from leukemia, to prolong the length of survival to comparable of healthy population and to attain a quality of life comparable to healthy people. Patients treated up-front with second generation TKIs (2GTKI) have a better chance to achieve faster and deeper response to therapy. Most of patients receiving 2GTKI in first line or e.g. nilotinib after initial phase of imatinib therapy can achieve very deep molecular response (MR4.5), which is a key criterion for discontinuation studies. The results of stop-trials suggest that substantial proportion of patient could achieve sustained treatment-free survival, and that the disease could be controlled despite of persistence of minimal residual disease, which does not require a clinical intervention. Patients group that could benefit most from discontinuation study include younger people, those who have achieved MR4.5 and patients reporting TKI – associated side effects. Achievement of MR4.5 could be considered as a target of CML therapy for considerable proportion of patients. The question of safe TKI dose reduction or therapy cessation should be addressed in the future planned clinical trials.
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