• François-Xavier Mahon, Carla Boquimpani, Dong-Wook Kim, Noam Benyamini, Nelma Cristina D Clementino, Vasily Shuvaev, Sikander Ailawadhi, Jeffrey Howard Lipton, Anna G Turkina, Raquel De Paz, Beatriz Moiraghi, Franck E Nicolini, Jolanta Dengler, Tomasz Sacha, Naoto Takahashi, Rafik Fellague-Chebra, Sandip Acharya, Stephane Wong, Yu Jin, and Timothy P Hughes.
• University of Bordeaux, Bordeaux, France (F.M.).
• Ann. Intern. Med. 2018 Apr 3; 168 (7): 461-470.

BackgroundTreatment-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).ObjectiveTo evaluate TFR after discontinuation of second-line nilotinib therapy.DesignSingle-group, phase 2, open-label study. (ClinicalTrials.gov: NCT01698905).Setting63 centers in 18 countries.PatientsAdults 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.InterventionsPatients 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.MeasurementsProportion of patients without loss of MMR, confirmed loss of MR4, or treatment reinitiation within 48 weeks of stopping treatment (primary end point).Results163 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.LimitationThe study included a heterogeneous patient population and was not designed to compare outcomes between patients continuing and those stopping treatment.ConclusionTFR seems achievable in patients with sustained MR4.5 after switching to nilotinib.Primary Funding SourceNovartis Pharmaceuticals Corporation.

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