Treatment-free remission after second-line nilotinib treatment in patients with chronic myeloid leukemia in chronic phase results from a single-group, phase 2, open-label study

François Xavier Mahon, Carla Boquimpani, Dong Wook Kim, Noam Benyamini, Nelma Cristina D. Clementino, Vasily Shuvaev, Sikander Ailawadhi, Jeffrey Howard Lipton, Anna G. Turkina, Raquel De Paz, Beatriz Moiraghi, Franck E. Nicolini, Jolanta Dengler, Tomasz Sacha, Naoto Takahashi, Rafik Fellague-Chebra, Sandip Acharya, Stephane Wong, Yu Jin, Timothy P. Hughes

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: Treatment-free remission (TFR) - that is, stopping tyrosine kinase inhibitor (TKI) therapy without loss of response - is an emerging treatment goal in chronic myeloid leukemia (CML). Objective: To evaluate TFR after discontinuation of second-line nilotinib therapy. Design: Single-group, phase 2, open-label study. (ClinicalTrials.gov: NCT01698905) Setting: 63 centers in 18 countries. Patients: Adults with CML in chronic phase who received TKI therapy for at least 3 years (>4 weeks with imatinib, then ≥2 years with nilotinib) and achieved MR4.5 (BCR-ABL1 ≤0.0032% on the International Scale [BCR-ABL1IS]) while receiving nilotinib entered a 1-year consolidation phase. Those with sustained MR4.5 during consolidation were eligible to enter TFR. Interventions: Patients received nilotinib during consolidation; those who entered TFR stopped treatment. Patients with loss of major molecular response (MMR) (BCR-ABL1IS ≤0.1%) or confirmed loss of MR4 (BCR-ABL1IS ≤0.01%) during TFR reinitiated nilotinib treatment. Measurements: Proportion of patients without loss of MMR, confirmed loss of MR4, or treatment reinitiation within 48 weeks of stopping treatment (primary end point). Results: 163 patients who had switched from imatinib to nilotinib (for reasons including resistance, intolerance, and physician preference) enrolled in the study and entered the consolidation phase. Of these patients, 126 met the criteria for entering the TFR phase, and 73 (58% [95% CI, 49% to 67%]) and 67 (53% [CI, 44% to 62%]) maintained TFR at 48 weeks (primary end point) and 96 weeks, respectively. Of the 56 patients who reinitiated nilotinib therapy, 55 regained MMR or better and 52 regained MR4.5. None had CML progression to accelerated phase or blast crisis. Musculoskeletal pain was more frequent during the first 48 weeks after nilotinib discontinuation. Limitation: The study included a heterogeneous patient population and was not designed to compare outcomes between patients continuing and those stopping treatment. Conclusion: TFR seems achievable in patients with sustained MR4.5 after switching to nilotinib.

Original languageEnglish (US)
Pages (from-to)461-470
Number of pages10
JournalAnnals of Internal Medicine
Volume168
Issue number7
DOIs
StatePublished - Apr 3 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
Protein-Tyrosine Kinases
Blast Crisis
Musculoskeletal Pain

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Treatment-free remission after second-line nilotinib treatment in patients with chronic myeloid leukemia in chronic phase results from a single-group, phase 2, open-label study. / Mahon, François Xavier; Boquimpani, Carla; Kim, Dong Wook; Benyamini, Noam; Clementino, Nelma Cristina D.; Shuvaev, Vasily; Ailawadhi, Sikander; Lipton, Jeffrey Howard; Turkina, Anna G.; De Paz, Raquel; Moiraghi, Beatriz; Nicolini, Franck E.; Dengler, Jolanta; Sacha, Tomasz; Takahashi, Naoto; Fellague-Chebra, Rafik; Acharya, Sandip; Wong, Stephane; Jin, Yu; Hughes, Timothy P.

In: Annals of Internal Medicine, Vol. 168, No. 7, 03.04.2018, p. 461-470.

Research output: Contribution to journalArticle

Mahon, FX, Boquimpani, C, Kim, DW, Benyamini, N, Clementino, NCD, Shuvaev, V, Ailawadhi, S, Lipton, JH, Turkina, AG, De Paz, R, Moiraghi, B, Nicolini, FE, Dengler, J, Sacha, T, Takahashi, N, Fellague-Chebra, R, Acharya, S, Wong, S, Jin, Y & Hughes, TP 2018, 'Treatment-free remission after second-line nilotinib treatment in patients with chronic myeloid leukemia in chronic phase results from a single-group, phase 2, open-label study', Annals of Internal Medicine, vol. 168, no. 7, pp. 461-470. https://doi.org/10.7326/M17-1094
Mahon, François Xavier ; Boquimpani, Carla ; Kim, Dong Wook ; Benyamini, Noam ; Clementino, Nelma Cristina D. ; Shuvaev, Vasily ; Ailawadhi, Sikander ; Lipton, Jeffrey Howard ; Turkina, Anna G. ; De Paz, Raquel ; Moiraghi, Beatriz ; Nicolini, Franck E. ; Dengler, Jolanta ; Sacha, Tomasz ; Takahashi, Naoto ; Fellague-Chebra, Rafik ; Acharya, Sandip ; Wong, Stephane ; Jin, Yu ; Hughes, Timothy P. / Treatment-free remission after second-line nilotinib treatment in patients with chronic myeloid leukemia in chronic phase results from a single-group, phase 2, open-label study. In: Annals of Internal Medicine. 2018 ; Vol. 168, No. 7. pp. 461-470.
@article{eaceff102bf74503b274b230880db3f3,
title = "Treatment-free remission after second-line nilotinib treatment in patients with chronic myeloid leukemia in chronic phase results from a single-group, phase 2, open-label study",
abstract = "Background: Treatment-free remission (TFR) - that is, stopping tyrosine kinase inhibitor (TKI) therapy without loss of response - is an emerging treatment goal in chronic myeloid leukemia (CML). Objective: To evaluate TFR after discontinuation of second-line nilotinib therapy. Design: Single-group, phase 2, open-label study. (ClinicalTrials.gov: NCT01698905) Setting: 63 centers in 18 countries. Patients: Adults with CML in chronic phase who received TKI therapy for at least 3 years (>4 weeks with imatinib, then ≥2 years with nilotinib) and achieved MR4.5 (BCR-ABL1 ≤0.0032{\%} on the International Scale [BCR-ABL1IS]) while receiving nilotinib entered a 1-year consolidation phase. Those with sustained MR4.5 during consolidation were eligible to enter TFR. Interventions: Patients received nilotinib during consolidation; those who entered TFR stopped treatment. Patients with loss of major molecular response (MMR) (BCR-ABL1IS ≤0.1{\%}) or confirmed loss of MR4 (BCR-ABL1IS ≤0.01{\%}) during TFR reinitiated nilotinib treatment. Measurements: Proportion of patients without loss of MMR, confirmed loss of MR4, or treatment reinitiation within 48 weeks of stopping treatment (primary end point). Results: 163 patients who had switched from imatinib to nilotinib (for reasons including resistance, intolerance, and physician preference) enrolled in the study and entered the consolidation phase. Of these patients, 126 met the criteria for entering the TFR phase, and 73 (58{\%} [95{\%} CI, 49{\%} to 67{\%}]) and 67 (53{\%} [CI, 44{\%} to 62{\%}]) maintained TFR at 48 weeks (primary end point) and 96 weeks, respectively. Of the 56 patients who reinitiated nilotinib therapy, 55 regained MMR or better and 52 regained MR4.5. None had CML progression to accelerated phase or blast crisis. Musculoskeletal pain was more frequent during the first 48 weeks after nilotinib discontinuation. Limitation: The study included a heterogeneous patient population and was not designed to compare outcomes between patients continuing and those stopping treatment. Conclusion: TFR seems achievable in patients with sustained MR4.5 after switching to nilotinib.",
author = "Mahon, {Fran{\cc}ois Xavier} and Carla Boquimpani and Kim, {Dong Wook} and Noam Benyamini and Clementino, {Nelma Cristina D.} and Vasily Shuvaev and Sikander Ailawadhi and Lipton, {Jeffrey Howard} and Turkina, {Anna G.} and {De Paz}, Raquel and Beatriz Moiraghi and Nicolini, {Franck E.} and Jolanta Dengler and Tomasz Sacha and Naoto Takahashi and Rafik Fellague-Chebra and Sandip Acharya and Stephane Wong and Yu Jin and Hughes, {Timothy P.}",
year = "2018",
month = "4",
day = "3",
doi = "10.7326/M17-1094",
language = "English (US)",
volume = "168",
pages = "461--470",
journal = "Annals of Internal Medicine",
issn = "0003-4819",
publisher = "American College of Physicians",
number = "7",

}

TY - JOUR

T1 - Treatment-free remission after second-line nilotinib treatment in patients with chronic myeloid leukemia in chronic phase results from a single-group, phase 2, open-label study

AU - Mahon, François Xavier

AU - Boquimpani, Carla

AU - Kim, Dong Wook

AU - Benyamini, Noam

AU - Clementino, Nelma Cristina D.

AU - Shuvaev, Vasily

AU - Ailawadhi, Sikander

AU - Lipton, Jeffrey Howard

AU - Turkina, Anna G.

AU - De Paz, Raquel

AU - Moiraghi, Beatriz

AU - Nicolini, Franck E.

AU - Dengler, Jolanta

AU - Sacha, Tomasz

AU - Takahashi, Naoto

AU - Fellague-Chebra, Rafik

AU - Acharya, Sandip

AU - Wong, Stephane

AU - Jin, Yu

AU - Hughes, Timothy P.

PY - 2018/4/3

Y1 - 2018/4/3

N2 - Background: Treatment-free remission (TFR) - that is, stopping tyrosine kinase inhibitor (TKI) therapy without loss of response - is an emerging treatment goal in chronic myeloid leukemia (CML). Objective: To evaluate TFR after discontinuation of second-line nilotinib therapy. Design: Single-group, phase 2, open-label study. (ClinicalTrials.gov: NCT01698905) Setting: 63 centers in 18 countries. Patients: Adults with CML in chronic phase who received TKI therapy for at least 3 years (>4 weeks with imatinib, then ≥2 years with nilotinib) and achieved MR4.5 (BCR-ABL1 ≤0.0032% on the International Scale [BCR-ABL1IS]) while receiving nilotinib entered a 1-year consolidation phase. Those with sustained MR4.5 during consolidation were eligible to enter TFR. Interventions: Patients received nilotinib during consolidation; those who entered TFR stopped treatment. Patients with loss of major molecular response (MMR) (BCR-ABL1IS ≤0.1%) or confirmed loss of MR4 (BCR-ABL1IS ≤0.01%) during TFR reinitiated nilotinib treatment. Measurements: Proportion of patients without loss of MMR, confirmed loss of MR4, or treatment reinitiation within 48 weeks of stopping treatment (primary end point). Results: 163 patients who had switched from imatinib to nilotinib (for reasons including resistance, intolerance, and physician preference) enrolled in the study and entered the consolidation phase. Of these patients, 126 met the criteria for entering the TFR phase, and 73 (58% [95% CI, 49% to 67%]) and 67 (53% [CI, 44% to 62%]) maintained TFR at 48 weeks (primary end point) and 96 weeks, respectively. Of the 56 patients who reinitiated nilotinib therapy, 55 regained MMR or better and 52 regained MR4.5. None had CML progression to accelerated phase or blast crisis. Musculoskeletal pain was more frequent during the first 48 weeks after nilotinib discontinuation. Limitation: The study included a heterogeneous patient population and was not designed to compare outcomes between patients continuing and those stopping treatment. Conclusion: TFR seems achievable in patients with sustained MR4.5 after switching to nilotinib.

AB - Background: Treatment-free remission (TFR) - that is, stopping tyrosine kinase inhibitor (TKI) therapy without loss of response - is an emerging treatment goal in chronic myeloid leukemia (CML). Objective: To evaluate TFR after discontinuation of second-line nilotinib therapy. Design: Single-group, phase 2, open-label study. (ClinicalTrials.gov: NCT01698905) Setting: 63 centers in 18 countries. Patients: Adults with CML in chronic phase who received TKI therapy for at least 3 years (>4 weeks with imatinib, then ≥2 years with nilotinib) and achieved MR4.5 (BCR-ABL1 ≤0.0032% on the International Scale [BCR-ABL1IS]) while receiving nilotinib entered a 1-year consolidation phase. Those with sustained MR4.5 during consolidation were eligible to enter TFR. Interventions: Patients received nilotinib during consolidation; those who entered TFR stopped treatment. Patients with loss of major molecular response (MMR) (BCR-ABL1IS ≤0.1%) or confirmed loss of MR4 (BCR-ABL1IS ≤0.01%) during TFR reinitiated nilotinib treatment. Measurements: Proportion of patients without loss of MMR, confirmed loss of MR4, or treatment reinitiation within 48 weeks of stopping treatment (primary end point). Results: 163 patients who had switched from imatinib to nilotinib (for reasons including resistance, intolerance, and physician preference) enrolled in the study and entered the consolidation phase. Of these patients, 126 met the criteria for entering the TFR phase, and 73 (58% [95% CI, 49% to 67%]) and 67 (53% [CI, 44% to 62%]) maintained TFR at 48 weeks (primary end point) and 96 weeks, respectively. Of the 56 patients who reinitiated nilotinib therapy, 55 regained MMR or better and 52 regained MR4.5. None had CML progression to accelerated phase or blast crisis. Musculoskeletal pain was more frequent during the first 48 weeks after nilotinib discontinuation. Limitation: The study included a heterogeneous patient population and was not designed to compare outcomes between patients continuing and those stopping treatment. Conclusion: TFR seems achievable in patients with sustained MR4.5 after switching to nilotinib.

UR - http://www.scopus.com/inward/record.url?scp=85045263918&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045263918&partnerID=8YFLogxK

U2 - 10.7326/M17-1094

DO - 10.7326/M17-1094

M3 - Article

C2 - 29459949

AN - SCOPUS:85045263918

VL - 168

SP - 461

EP - 470

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 7

ER -