Treatment-free remission following frontline nilotinib in patients with CML in chronic phase: results from the ENESTfreedom study

A Hochhaus1, T Masszi2, F J Giles3, J P Radich4, D M Ross5, M T Gómez Casares6, A Hellmann7, J Stentoft8, E Conneally9, V García-Gutiérrez10, N Gattermann11, W Wiktor-Jedrzejczak12, P D le Coutre13, B Martino14, S Saussele15, H D Menssen16, W Deng17, N Krunic18, V Bedoucha16 and G Saglio19

The single-arm, phase 2 ENESTfreedom trial assessed the potential for treatment-free remission (TFR; i.e., the ability to maintain a molecular response after stopping therapy) following frontline nilotinib treatment. Patients with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase with MR4.5 (BCR-ABL1less than or equal to0.0032% on the International Scale (BCR-ABL1IS)) and greater than or equal to2 years of frontline nilotinib therapy were enrolled. Patients with sustained deep molecular response during the 1-year nilotinib consolidation phase were eligible to stop treatment and enter the TFR phase. Patients with loss of major molecular response (MMR; BCR-ABL1ISless than or equal to0.1%) during the TFR phase reinitiated nilotinib. In total, 215 patients entered the consolidation phase, of whom 190 entered the TFR phase. The median duration of nilotinib before stopping treatment was 43.5 months. At 48 weeks after stopping nilotinib, 98 patients (51.6%; 95% confidence interval, 44.2–58.9%) remained in MMR or better (primary end point). Of the 86 patients who restarted nilotinib in the treatment reinitiation phase after the loss of MMR, 98.8% and 88.4%, respectively, regained MMR and MR4.5 by the data cutoff date. Consistent with prior reports of imatinib-treated patients, musculoskeletal pain-related events were reported in 24.7% of patients in the TFR phase (consolidation phase, 16.3%).

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