SAN DIEGO Some patients with chronic myeloid leukemia (CML) who have maintained deep molecular responses for at least 2 years can safely discontinue nilotinib, though relapse may occur even after more than 10 years of sustained deep molecular response, according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition.1

“Treatment-free remission is an emerging treatment goal for CML-chronic phase,” said Norimitsu Kadowaki, MD, PhD, department of internal medicine, division of hematology, rheumatology and respiratory medicine, Kagawa University, Japan. “In the STIM1 trial, 41% of patients maintained a deep molecular response after discontinuation of imatinib.”

To examine the safety and efficacy of nilotinib discontinuation and to identify predictive factors for successful discontinuation of nilotinib, researchers designed the Stop Nilotinib (NILSt) trial, a single-arm, phase 2 study.

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Investigators enrolled 114 patients with CML in chronic phase who achieved MR4.5 by treatment with imatinib or nilotinib and were treated with nilotinib for a further 2 years. Patients who maintained MR4.5 during those 2 years were eligible for discontinuation of nilotinib. Those who lost MR4.5 restarted nilotinib therapy.

The treatment-free remission rate 1 year after discontinuation of nilotinib was 62.2% (90% CI, 53.0-70.8).

Thirty-six patients experienced loss of MR4.5, with most occurring within 6 months of nilotinib discontinuation, though 34 of those achieved a second MR4.5 within a median of 2.2 months (95% CI, 1.5-2.6).

Age, sex, Sokal score, Hasford score, EUTOS score, history of interferon-alpha therapy, total duration of imatinib or nilotinib therapy, time to MR4.5, or trough concentrations of nilotinib in sera did not predict the likelihood of maintaining MR4.5 at 1 year after discontinuation.

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“Safe molecular response duration before discontinuation of nilotinib may be very long, or may not exist, in a substantial proportion of patients,” Dr Kadowaki said. “BCR-ABL kinase-independent pathways may need to be targeted for safe discontinuation in such patients in order to avoid serious adverse events and financial burden caused by prolonged administration.


  1. Kadowaki N, Kawaguchi T, Kuroda J, et al. Discontinuation of nilotinib in patients with chronic myeloid leukemia who have maintained deep molecular responses for at least 2 years: A multicenter phase 2 stop nilotinib (Nilst) Trial. Paper presented at: American Society of Hematology (ASH) 58th Annual Meeting and Exposition; December 3-6, 2016; San Diego, CA.