My burning issues in TKI therapy and treatment-free remission in CML

We all agree that treatment-free remission (TFR) is a common goal we aim for in cancer treatment. Even though many malignant diseases require long-term/maintenance therapies (i. e., IMiD maintenance in myeloma, antihormonal therapy in hormone-receptor-positive breast cancer or JAK inhibitors in myelofibrosis patients ineligible for allo-SCT), this often induces clinically relevant side effects lowering quality of life (QoL) and frequently also requires more intense clinical monitoring. For years, we also communicated the necessity of continuous life-long tyrosine kinase inhibitor (TKI) therapy to our patients with chronic myeloid leukemia (CML), until seminal work by F.X. Mahon and his French colleagues demonstrated that even though in some patients low-level disease burden fluctuates upon TKI withdrawal, approximately half of those patients can be successfully discontinued from targeted therapy for the long-term [1]. However, only a small proportion of optimal responders can continuously stop therapy (overall a maximum of 25% of chronic phase CML [CP-CML] patients treated up-front with 2nd generation TKIs are in long-term TFR). However, for me the following questions remain to be answered. …