The evolution of treatment-free remission

Abstract One of the most remarkable achievements of the tyrosine kinase inhibitor (TKI) era has been the capacity to induce deep molecular remissions that are sustainable off therapy in patients with chronic myeloid leukemia (CML), that is, treatment-free remission (TFR). TFR was first described in a handful of patients within 3 to 4 years of imatinib approval. In 2004, TFR was tested in a small French pilot study, followed soon after by the French STIM and Australasian TWISTER studies. These early trials demonstrated that TFR was achievable but also showed that rapid relapse was equally likely. Perhaps the most critical observation was that relapsing patients could be rapidly and safely returned to deep molecular remission after restarting therapy, minimizing the risk associated with TFR attempts. Consensus criteria for TFR eligibility were established soon after those studies were reported. Over the past decade, TFR criteria have been broadened, key predictive markers of success identified, and overall safety of TFR in the wider clinical community confirmed. Despite this progress, TFR is still only achieved in a fraction of patients with CML globally. Over the next decade, the focus will be making TFR the mainstream pathway for as many patients as possible as well as scaling back the duration of therapy required. More potent, better targeted TKIs, and immune modulation will likely have a significant impact. Predictive assays should enable most patients who attempt TFR to do so with a high probability of success. Ultimately TFR should be seen as the first step on an ambitious pathway toward cure for patients with CML.