Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in Chronic Phase : results From a Single-Group, Phase 2, Open-Label Study

Background Treatment-free remission (TFR)-that is, stopping tyrosine kinase inhibitor (TKI) therapy without loss of response-is an emerging treatment goal in chronic myeloid leukemia (CML). Objective To evaluate TFR after discontinuation of second-line nilotinib therapy. Design Single-group, phase 2, open-label study. (ClinicalTrials.gov: NCT01698905). Setting 63 centers in 18 countries. Patients Adults with CML in chronic phase who received TKI therapy for at least 3 years (>4 weeks with imatinib, then ≥2 years with nilotinib) and achieved MR4.5 (BCR-ABL1 ≤0.0032% on the International Scale [BCR-ABL1IS]) while receiving nilotinib entered a 1-year consolidation phase. Those with sustained MR4.5 during consolidation were eligible to enter TFR. Interventions Patients received nilotinib during consolidation; those who entered TFR stopped treatment. Patients with loss of major molecular response (MMR) (BCR-ABL1IS ≤0.1%) or confirmed loss of MR4 (BCR-ABL1IS ≤0.01%) during TFR reinitiated nilotinib treatment. Measurements Proportion of patients without loss of MMR, confirmed loss of MR4, or treatment reinitiation within 48 weeks of stopping treatment (primary end point). Results 163 patients who had switched from imatinib to nilotinib (for reasons including resistance, intolerance, and physician preference) enrolled in the study and entered the consolidation phase. Of these patients, 126 met the criteria for entering the TFR phase, and 73 (58% [95% CI, 49% to 67%]) and 67 (53% [CI, 44% to 62%]) maintained TFR at 48 weeks (primary end point) and 96 weeks, respectively. Of the 56 patients who reinitiated nilotinib therapy, 55 regained MMR or better and 52 regained MR4.5. None had CML progression to accelerated phase or blast crisis. Musculoskeletal pain was more frequent during the first 48 weeks after nilotinib discontinuation. Limitation The study included a heterogeneous patient population and was not designed to compare outcomes between patients continuing and those stopping treatment. Conclusion TFR seems achievable in patients with sustained MR4.5 after switching to nilotinib. Primary funding source Novartis Pharmaceuticals Corporation.