PMID- 33707652
OWN - NLM
STAT- MEDLINE
DCOM- 20210614
LR  - 20220719
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 35
IP  - 5
DP  - 2021 May
TI  - Treatment-free remission following frontline nilotinib in patients with chronic 
      phase chronic myeloid leukemia: 5-year update of the ENESTfreedom trial.
PG  - 1344-1355
LID - 10.1038/s41375-021-01205-5 [doi]
AB  - The ENESTfreedom trial assessed the feasibility of treatment-free remission (TFR) 
      in patients with chronic myeloid leukemia in chronic phase (CML-CP) following 
      frontline nilotinib treatment. Results for long-term outcomes after a 5-year 
      follow-up are presented herein. Patients who had received >/=2 years of frontline 
      nilotinib therapy and achieved MR(4.5) underwent a 1-year nilotinib treatment 
      consolidation phase before attempting TFR. At the 5-year data cut-off, 81/190 
      patients entering the TFR phase (42.6%) were still in TFR, with 76 (40.0%) in 
      MR(4.5). Patients who lost major molecular response (MMR) entered a treatment 
      re-initiation phase; 90/91 patients entering this phase (98.9%) regained MMR and 
      84/91 patients (92.3%) regained MR(4.5). The Kaplan-Meier estimated 
      treatment-free survival rate at 5 years was 48.2%. No disease progression or 
      CML-related deaths were reported. Whereas the incidence of adverse events (AEs) 
      declined from 96 weeks following the start of TFR, an increase in AE frequency 
      was observed for patients in the treatment re-initiation phase. Low Sokal risk 
      score, BCR-ABL1(IS) levels at 48 weeks of TFR and stable MR(4.5) response for the 
      first year of TFR were associated with higher TFR rates. Overall, these results 
      support the efficacy and safety of attempting TFR following upfront nilotinib 
      therapy of >3 years in patients with CML-CP.
FAU - Radich, Jerald P
AU  - Radich JP
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 
      USA.
FAU - Hochhaus, Andreas
AU  - Hochhaus A
AD  - Abteilung Hamatologie/Onkologie, Universitatsklinikum Jena, Jena, Germany.
FAU - Masszi, Tamas
AU  - Masszi T
AUID- ORCID: 0000-0003-2322-9863
AD  - Semmelweis University, Budapest, Hungary.
FAU - Hellmann, Andrzej
AU  - Hellmann A
AD  - Medical University of Gdansk, Gdansk, Poland.
FAU - Stentoft, Jesper
AU  - Stentoft J
AD  - Aarhus University Hospital, Aarhus, Denmark.
FAU - Casares, Maria Teresa Gomez
AU  - Casares MTG
AD  - Hospital Universitario de Gran Canaria Dr Negrin, Las Palmas de Gran Canaria, 
      Spain.
FAU - Garcia-Gutierrez, J Valentin
AU  - Garcia-Gutierrez JV
AUID- ORCID: 0000-0003-4752-0815
AD  - Hospital Universitario Ramon y Cajal, IRYCIS, Madrid, Spain.
FAU - Conneally, Eibhlin
AU  - Conneally E
AD  - St James's Hospital, Dublin, Ireland.
FAU - le Coutre, Philipp D
AU  - le Coutre PD
AD  - Charite-Universitatsmedizin Berlin, Berlin, Germany.
FAU - Gattermann, Norbert
AU  - Gattermann N
AD  - Universitatsklinikum Dusseldorf, Dusseldorf, Germany.
FAU - Martino, Bruno
AU  - Martino B
AD  - Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio Calabria, Italy.
FAU - Saussele, Susanne
AU  - Saussele S
AUID- ORCID: 0000-0003-0357-5785
AD  - III. Med. Klinik, Medizinische Fakultat Mannheim der Universitat Heidelberg, 
      Mannheim, Germany.
FAU - Giles, Francis J
AU  - Giles FJ
AD  - Developmental Therapeutics Consortium, Chicago, IL, USA.
FAU - Ross, David M
AU  - Ross DM
AUID- ORCID: 0000-0001-7171-2935
AD  - Division of Haematology, SA Pathology, Royal Adelaide Hospital, Adelaide, 
      Australia.
FAU - Aimone, Paola
AU  - Aimone P
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Li, Sai
AU  - Li S
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Titorenko, Ksenia
AU  - Titorenko K
AUID- ORCID: 0000-0002-5379-388X
AD  - Novartis Pharmaceuticals Corporation, Moscow, Russian Federation.
FAU - Saglio, Giuseppe
AU  - Saglio G
AUID- ORCID: 0000-0002-1046-3514
AD  - University of Turin, Orbassano, Italy. giuseppe.saglio@unito.it.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20210311
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - F41401512X (nilotinib)
SB  - IM
MH  - Adolescent
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy/mortality
MH  - Leukemia, Myeloid, Chronic-Phase/*drug therapy/mortality
MH  - Male
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Pyrimidines/*therapeutic use
MH  - Survival Rate
MH  - Treatment Outcome
PMC - PMC8102196
COIS- JPR has received research funding from Novartis and provided consulting to 
      Novartis, Amgen, Bristol-Myers Squibb, and Jazz. AHo has received research 
      funding from Novartis, Bristol-Myers Squibb, Incyte, MSD, and Pfizer, and 
      honoraria from Bristol-Myers Squibb, Novartis, Pfizer, and Takeda. TM has 
      participated in advisory board meetings for AbbVie, Bristol-Myers Squibb, 
      Janssen, Novartis, Pfizer, and Takeda. JVGG has received honoraria and research 
      funding and has provided consulting to Novartis, Bristol-Myers Squibb, Incyte, 
      and Pfizer. EC has received research funding from and provided consulting to 
      Novartis and received honoraria from Bristol-Myers Squibb, Gilead, and Pfizer. 
      PDLC has received honoraria from Novartis, Incyte, and Pfizer. NG has received 
      research funding, lecture honoraria, and travel support from Novartis. SS has 
      received research funding and honoraria from Novartis, Bristol-Myers Squibb, and 
      Incyte, and honoraria from Pfizer. FJG has received research funding from 
      Novartis and Pfizer, and provided consulting to Novartis and Actuate Therapeutics 
      Inc. DMR has received research funding and honoraria from and participated in 
      advisory boards for Novartis and received honoraria from Bristol-Myers Squibb and 
      research funding from Celgene. GS has received research funding from Novartis, 
      Ariad, Bristol-Myers Squibb, Incyte, Pfizer, and Roche. PA, SL, and KT are 
      employed by Novartis. AHe, JS, MTGC, and BM declare that they have no conflicts 
      of interest. This study was sponsored and funded by Novartis Pharmaceuticals.
EDAT- 2021/03/13 06:00
MHDA- 2021/06/16 06:00
PMCR- 2021/03/11
CRDT- 2021/03/12 07:03
PHST- 2020/11/17 00:00 [received]
PHST- 2021/02/18 00:00 [accepted]
PHST- 2021/02/01 00:00 [revised]
PHST- 2021/03/13 06:00 [pubmed]
PHST- 2021/06/16 06:00 [medline]
PHST- 2021/03/12 07:03 [entrez]
PHST- 2021/03/11 00:00 [pmc-release]
AID - 10.1038/s41375-021-01205-5 [pii]
AID - 1205 [pii]
AID - 10.1038/s41375-021-01205-5 [doi]
PST - ppublish
SO  - Leukemia. 2021 May;35(5):1344-1355. doi: 10.1038/s41375-021-01205-5. Epub 2021 
      Mar 11.