TY - JOUR

T1 - Long-term treatment-free remission in patients with chronic myeloid leukemia after second-line nilotinib

T2 - ENESTop 5-year update

AU - Hughes, Timothy P

AU - Clementino, Nelma Cristina D

AU - Fominykh, Mikhail

AU - Lipton, Jeffrey H

AU - Turkina, Anna G

AU - Moiraghi, Elena Beatriz

AU - Nicolini, Franck E

AU - Takahashi, Naoto

AU - Sacha, Tomasz

AU - Kim, Dong-Wook

AU - Fellague-Chebra, Rafik

AU - Tiwari, Ranjan

AU - Bouard, Catherine

AU - Mahon, Francois-Xavier

N1 - Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2021/6

Y1 - 2021/6

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Clinical Trials, Phase II as Topic

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy

KW - Long-Term Care/methods

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Prospective Studies

KW - Pyrimidines/therapeutic use

KW - Remission Induction

KW - Survival Rate

KW - MAJOR MOLECULAR RESPONSE

KW - DISCONTINUATION

KW - TYROSINE KINASE INHIBITORS

KW - THERAPY

KW - IMATINIB

UR - http://www.scopus.com/inward/record.url?scp=85105811703&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/e749cb23-a975-3889-a0ee-420d6688c193/

U2 - 10.1038/s41375-021-01260-y

DO - 10.1038/s41375-021-01260-y

M3 - Article

C2 - 33980976

VL - 35

SP - 1631

EP - 1642

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 6

ER -