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, T. 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

Research output: Article

23 Citations (Scopus)

Abstract

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)1-10
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
DOIs
Publication statusAccepted/In press - febr. 22 2018

Fingerprint

Leukemia, Myeloid, Chronic Phase
Therapeutics
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Disease Progression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib : 96-week update of the ENESTfreedom study. / Ross, David M.; Masszi, T.; Gómez Casares, María Teresa; Hellmann, Andrzej; Stentoft, Jesper; Conneally, Eibhlin; Garcia-Gutierrez, Valentin; Gattermann, Norbert; Le Coutre, Philipp D.; Martino, Bruno; Saussele, Susanne; Giles, Francis J.; Radich, Jerald P.; Saglio, Giuseppe; Deng, Weiping; Krunic, Nancy; Bédoucha, Véronique; Gopalakrishna, Prashanth; Hochhaus, Andreas.

In: Journal of Cancer Research and Clinical Oncology, 22.02.2018, p. 1-10.

Research output: Article

Ross, DM, Masszi, T, Gómez Casares, MT, Hellmann, A, Stentoft, J, Conneally, E, Garcia-Gutierrez, V, Gattermann, N, Le Coutre, PD, Martino, B, Saussele, S, Giles, FJ, Radich, JP, Saglio, G, Deng, W, Krunic, N, Bédoucha, V, Gopalakrishna, P & Hochhaus, A 2018, 'Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib: 96-week update of the ENESTfreedom study', Journal of Cancer Research and Clinical Oncology, pp. 1-10. https://doi.org/10.1007/s00432-018-2604-x
Ross, David M. ; Masszi, T. ; Gómez Casares, María Teresa ; Hellmann, Andrzej ; Stentoft, Jesper ; Conneally, Eibhlin ; Garcia-Gutierrez, Valentin ; Gattermann, Norbert ; Le Coutre, Philipp D. ; Martino, Bruno ; Saussele, Susanne ; Giles, Francis J. ; Radich, Jerald P. ; Saglio, Giuseppe ; Deng, Weiping ; Krunic, Nancy ; Bédoucha, Véronique ; Gopalakrishna, Prashanth ; Hochhaus, Andreas. / Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib : 96-week update of the ENESTfreedom study. In: Journal of Cancer Research and Clinical Oncology. 2018 ; pp. 1-10.
@article{385b25cd18bc4491a08bfb24e9a4cd4c,
title = "Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib: 96-week update of the ENESTfreedom study",
abstract = "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.",
keywords = "Chronic myeloid leukemia, Clinical trial, Frontline, Nilotinib, Predictors of TFR, Treatment-free remission",
author = "Ross, {David M.} and T. Masszi and {G{\'o}mez Casares}, {Mar{\'i}a Teresa} and Andrzej Hellmann and Jesper Stentoft and Eibhlin Conneally and Valentin Garcia-Gutierrez and Norbert Gattermann and {Le Coutre}, {Philipp D.} and Bruno Martino and Susanne Saussele and Giles, {Francis J.} and Radich, {Jerald P.} and Giuseppe Saglio and Weiping Deng and Nancy Krunic and V{\'e}ronique B{\'e}doucha and Prashanth Gopalakrishna and Andreas Hochhaus",
year = "2018",
month = "2",
day = "22",
doi = "10.1007/s00432-018-2604-x",
language = "English",
pages = "1--10",
journal = "Zeitschrift fur Krebsforschung und Klinische Onkologie",
issn = "0171-5216",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib

T2 - 96-week update of the ENESTfreedom study

AU - Ross, David M.

AU - Masszi, T.

AU - Gómez Casares, María Teresa

AU - Hellmann, Andrzej

AU - Stentoft, Jesper

AU - Conneally, Eibhlin

AU - Garcia-Gutierrez, Valentin

AU - Gattermann, Norbert

AU - Le Coutre, Philipp D.

AU - Martino, Bruno

AU - Saussele, Susanne

AU - Giles, Francis J.

AU - Radich, Jerald P.

AU - Saglio, Giuseppe

AU - Deng, Weiping

AU - Krunic, Nancy

AU - Bédoucha, Véronique

AU - Gopalakrishna, Prashanth

AU - Hochhaus, Andreas

PY - 2018/2/22

Y1 - 2018/2/22

N2 - 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.

AB - 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.

KW - Chronic myeloid leukemia

KW - Clinical trial

KW - Frontline

KW - Nilotinib

KW - Predictors of TFR

KW - Treatment-free remission

UR - http://www.scopus.com/inward/record.url?scp=85042212112&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042212112&partnerID=8YFLogxK

U2 - 10.1007/s00432-018-2604-x

DO - 10.1007/s00432-018-2604-x

M3 - Article

C2 - 29468438

AN - SCOPUS:85042212112

SP - 1

EP - 10

JO - Zeitschrift fur Krebsforschung und Klinische Onkologie

JF - Zeitschrift fur Krebsforschung und Klinische Onkologie

SN - 0171-5216

ER -