Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib: 96-week update of the ENESTfreedom study

David M. Ross, Tamas Masszi, María Teresa Gómez Casares, Andrzej Hellmann, Jesper Stentoft, Eibhlin Conneally, Valentin Garcia-Gutierrez, Norbert Gattermann, Philipp D. le Coutre, Bruno Martino, Susanne Saussele, Francis J. Giles, Jerald P. Radich, Giuseppe Saglio, Weiping Deng, Nancy Krunic, Véronique Bédoucha, Prashanth Gopalakrishna, Andreas Hochhaus

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Purpose: ENESTfreedom is evaluating treatment-free remission (TFR) following frontline nilotinib in patients with chronic myeloid leukemia (CML) in chronic phase. Following our primary analysis at 48 weeks, we here provide an updated 96-week analysis. Methods: Attempting TFR required ≥ 3 years of nilotinib, a molecular response of MR4.5 [BCR-ABL1 ≤ 0.0032% on the International Scale (BCR-ABL1IS)], and sustained deep molecular response (DMR) during a 1-year consolidation phase. Patients restarted nilotinib following loss of major molecular response (MMR; BCR-ABL1IS ≤ 0.1%). Results: Ninety-six weeks after stopping treatment (3.6-year median prior nilotinib duration), 93 of 190 patients (48.9%) remained in TFR. Of 88 patients who restarted nilotinib following loss of MMR, 87 regained MMR and 81 regained MR4.5 by the data cut-off. Ninety-six-week TFR rates were 61.3, 50.0, and 28.6% in patients with low, intermediate, and high Sokal risk scores at diagnosis, respectively. Patients consistently in MR4.5 during consolidation had higher TFR rates (50.6%) than patients with ≥ 1 assessment without MR4.5 during consolidation (35.0%). In a landmark analysis, 96-week TFR rates for patients with MR4.5, MR4 (BCR-ABL1IS ≤ 0.01%) but not MR4.5, and MMR but not MR4 at TFR week 12 were 82.6, 23.1, and 0%, respectively. There were no reports of disease progression or death due to CML; overall adverse event frequency decreased following TFR. Within the follow-up period, TFR did not adversely affect disease outcomes. Conclusions: These results demonstrate the feasibility and durability of TFR following frontline nilotinib and emphasize the importance of sustained DMR for TFR.

Original languageEnglish
Pages (from-to)945-954
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Issue number5
Publication statusPublished or Issued - 1 May 2018


  • Chronic myeloid leukemia
  • Clinical trial
  • Frontline
  • Nilotinib
  • Predictors of TFR
  • Treatment-free remission

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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