The ENESTop study evaluated treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML) in chronic phase who had received ≥3 years of tyrosine kinase inhibitor therapy and achieved sustained deep molecular response only after switching from imatinib to nilotinib. After 1-year nilotinib consolidation, 126 patients attempted TFR. At 48 weeks (primary analysis), 57.9% (73/126) were in TFR. In the present analysis at 5 years, 42.9% (54/126) were in TFR. Since the 48-week analysis, among patients who left the TFR phase, 58% (11/19) did not have a loss of molecular response and discontinued for other reasons. Of the 59 patients who reinitiated nilotinib upon loss of major molecular response (MMR) or confirmed loss of MR4, 98.3% regained MMR, 94.9% regained MR4, and 93.2% regained MR4.5. Overall adverse event rates decreased over the 5 years of TFR. In patients reinitiating nilotinib, there was a cumulative increase in cardiovascular events with longer nilotinib exposure. No disease progression or CML-related deaths were reported. Overall, these results confirm the durability and safety of TFR for patients receiving second-line nilotinib. Cardiovascular risk should be carefully managed, particularly when reinitiating treatment after TFR.
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The authors would like to thank all study sites and participating countries, the study investigators, and all study participants and their families. The authors also thank Tim Harries of Novartis Pharmaceuticals UK Ltd, London, UK, for providing medical editorial assistance. This study was sponsored and funded by Novartis Pharmaceuticals.
Conflict of interest
TPH has received honoraria and research funding from and is a member of a board of directors or advisory committee at Bristol-Myers Squibb and Novartis. NDC has received financial support for congresses from EMS. MF has received honoraria from and is a member of a speakers bureau for BMS, Novartis and Pfizer. JHL has received research funding from and provided consulting to Ariad, Bristol-Myers Squibb, Novartis and Pfizer. AGT has received honoraria from Bristol-Myers Squibb, Novartis, and Pfizer. BM is a member of a speakers bureau for Bristol-Myers Squibb and Novartis. FEN has received honoraria and research funding from Incyte Biosciences and Novartis, and provided consultancy to Analysis Group Inc. and Sun Pharma. NT has received honoraria from Bristol-Myers Squibb, Novartis Pharma KK and Pfizer Japan Inc., and research funding from Novartis Pharma KK and Pfizer Japan Inc. TS has provided consultancy to and received honoraria and research funding from Bristol-Myers Squibb, Incyte, Novartis and Pfizer, and provided consultancy to and received honoraria from Adamed. DWK has received honoraria and research funding from Bristol-Myers Squibb, ILYANG, Novartis and Pfizer, is a member of a speakers bureau for Bristol-Myers Squibb, Novartis and Pfizer, is a member of a board of directors or advisory committee at Bristol-Myers Squibb and Pfizer, and has provided consultancy for ILYANG and Novartis. RFC is employed by, is an equity holder in and has received research funding from Novartis. RT and CB are employed by Novartis. FXM h0as received honoraria from ARIAD, Bristol-Myers Squibb, Novartis and Pfizer, and has received research funding from Novartis. This study was sponsored and funded by Novartis Pharmaceuticals.
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Hughes, T.P., Clementino, N.C.D., Fominykh, M. et al. Long-term treatment-free remission in patients with chronic myeloid leukemia after second-line nilotinib: ENESTop 5-year update. Leukemia 35, 1631–1642 (2021). https://doi.org/10.1038/s41375-021-01260-y
Current Hematologic Malignancy Reports (2021)