Cessation of nilotinib in patients with chronic myelogenous leukemia who have maintained deep molecular responses for 2 years: a multicenter phase 2 trial, stop nilotinib (NILSt)

Koji Nagafuji, Itaru Matsumura, Takayuki Shimose, Tatsuya Kawaguchi, Junya Kuroda, Hirohisa Nakamae, Toshihiro Miyamoto, Norimitsu Kadowaki, Jun Ishikawa, Yutaka Imamura, Hirohito Yamazaki, Koichi Akashi, Yuzuru Kanakura

研究成果: ジャーナルへの寄稿記事

抄録

The aim of this multicenter phase 2 trial, Stop Nilotinib (NILSt), was to examine the safety and efficacy of discontinuation of nilotinib in patients with chronic phase (CP)-chronic myelogenous leukemia (CML). Patients with CP-CML who had achieved molecular response (MR4.5) after initiation of imatinib or nilotinib therapy received consolidation therapy with nilotinib 300–400 mg twice daily for up to 24 months. Patients who maintained MR4.5 at 24 months of consolidation therapy proceeded to discontinuation of nilotinib. The study enrolled 149 patients; 112 patients proceeded to consolidation therapy with nilotinib; 90 patients maintained MR4.5 with consolidation therapy, and 87 proceeded to discontinuation of nilotinib. The treatment-free remission (TFR) (MR4.5) rate at both 1 and 3 years after discontinuation of nilotinib was the same, at 60.9% (90% CI 51.6–69.7). Among 34 patients with molecular relapse, nilotinib was resumed in 33 patients; all of them attained MR4.5. There was no significant association between molecular relapse and age, sex, Sokal score, previous interferon-α exposure, duration of tyrosine kinase inhibitors treatment, or trough concentration of nilotinib. With nilotinib, it might be possible to avoid prognostic factors for TFR that exist with imatinib discontinuation. Cessation of nilotinib after two years of consolidation was safe and feasible. Trial registration UMIN000007141.

元の言語英語
ページ(範囲)675-682
ページ数8
ジャーナルInternational journal of hematology
110
発行部数6
DOI
出版物ステータス出版済み - 12 1 2019

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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
Recurrence
Protein-Tyrosine Kinases
Interferons
Safety

All Science Journal Classification (ASJC) codes

  • Hematology

これを引用

Cessation of nilotinib in patients with chronic myelogenous leukemia who have maintained deep molecular responses for 2 years : a multicenter phase 2 trial, stop nilotinib (NILSt). / Nagafuji, Koji; Matsumura, Itaru; Shimose, Takayuki; Kawaguchi, Tatsuya; Kuroda, Junya; Nakamae, Hirohisa; Miyamoto, Toshihiro; Kadowaki, Norimitsu; Ishikawa, Jun; Imamura, Yutaka; Yamazaki, Hirohito; Akashi, Koichi; Kanakura, Yuzuru.

:: International journal of hematology, 巻 110, 番号 6, 01.12.2019, p. 675-682.

研究成果: ジャーナルへの寄稿記事

Nagafuji, Koji ; Matsumura, Itaru ; Shimose, Takayuki ; Kawaguchi, Tatsuya ; Kuroda, Junya ; Nakamae, Hirohisa ; Miyamoto, Toshihiro ; Kadowaki, Norimitsu ; Ishikawa, Jun ; Imamura, Yutaka ; Yamazaki, Hirohito ; Akashi, Koichi ; Kanakura, Yuzuru. / Cessation of nilotinib in patients with chronic myelogenous leukemia who have maintained deep molecular responses for 2 years : a multicenter phase 2 trial, stop nilotinib (NILSt). :: International journal of hematology. 2019 ; 巻 110, 番号 6. pp. 675-682.
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abstract = "The aim of this multicenter phase 2 trial, Stop Nilotinib (NILSt), was to examine the safety and efficacy of discontinuation of nilotinib in patients with chronic phase (CP)-chronic myelogenous leukemia (CML). Patients with CP-CML who had achieved molecular response (MR4.5) after initiation of imatinib or nilotinib therapy received consolidation therapy with nilotinib 300–400 mg twice daily for up to 24 months. Patients who maintained MR4.5 at 24 months of consolidation therapy proceeded to discontinuation of nilotinib. The study enrolled 149 patients; 112 patients proceeded to consolidation therapy with nilotinib; 90 patients maintained MR4.5 with consolidation therapy, and 87 proceeded to discontinuation of nilotinib. The treatment-free remission (TFR) (MR4.5) rate at both 1 and 3 years after discontinuation of nilotinib was the same, at 60.9{\%} (90{\%} CI 51.6–69.7). Among 34 patients with molecular relapse, nilotinib was resumed in 33 patients; all of them attained MR4.5. There was no significant association between molecular relapse and age, sex, Sokal score, previous interferon-α exposure, duration of tyrosine kinase inhibitors treatment, or trough concentration of nilotinib. With nilotinib, it might be possible to avoid prognostic factors for TFR that exist with imatinib discontinuation. Cessation of nilotinib after two years of consolidation was safe and feasible. Trial registration UMIN000007141.",
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T1 - Cessation of nilotinib in patients with chronic myelogenous leukemia who have maintained deep molecular responses for 2 years

T2 - a multicenter phase 2 trial, stop nilotinib (NILSt)

AU - Nagafuji, Koji

AU - Matsumura, Itaru

AU - Shimose, Takayuki

AU - Kawaguchi, Tatsuya

AU - Kuroda, Junya

AU - Nakamae, Hirohisa

AU - Miyamoto, Toshihiro

AU - Kadowaki, Norimitsu

AU - Ishikawa, Jun

AU - Imamura, Yutaka

AU - Yamazaki, Hirohito

AU - Akashi, Koichi

AU - Kanakura, Yuzuru

PY - 2019/12/1

Y1 - 2019/12/1

N2 - The aim of this multicenter phase 2 trial, Stop Nilotinib (NILSt), was to examine the safety and efficacy of discontinuation of nilotinib in patients with chronic phase (CP)-chronic myelogenous leukemia (CML). Patients with CP-CML who had achieved molecular response (MR4.5) after initiation of imatinib or nilotinib therapy received consolidation therapy with nilotinib 300–400 mg twice daily for up to 24 months. Patients who maintained MR4.5 at 24 months of consolidation therapy proceeded to discontinuation of nilotinib. The study enrolled 149 patients; 112 patients proceeded to consolidation therapy with nilotinib; 90 patients maintained MR4.5 with consolidation therapy, and 87 proceeded to discontinuation of nilotinib. The treatment-free remission (TFR) (MR4.5) rate at both 1 and 3 years after discontinuation of nilotinib was the same, at 60.9% (90% CI 51.6–69.7). Among 34 patients with molecular relapse, nilotinib was resumed in 33 patients; all of them attained MR4.5. There was no significant association between molecular relapse and age, sex, Sokal score, previous interferon-α exposure, duration of tyrosine kinase inhibitors treatment, or trough concentration of nilotinib. With nilotinib, it might be possible to avoid prognostic factors for TFR that exist with imatinib discontinuation. Cessation of nilotinib after two years of consolidation was safe and feasible. Trial registration UMIN000007141.

AB - The aim of this multicenter phase 2 trial, Stop Nilotinib (NILSt), was to examine the safety and efficacy of discontinuation of nilotinib in patients with chronic phase (CP)-chronic myelogenous leukemia (CML). Patients with CP-CML who had achieved molecular response (MR4.5) after initiation of imatinib or nilotinib therapy received consolidation therapy with nilotinib 300–400 mg twice daily for up to 24 months. Patients who maintained MR4.5 at 24 months of consolidation therapy proceeded to discontinuation of nilotinib. The study enrolled 149 patients; 112 patients proceeded to consolidation therapy with nilotinib; 90 patients maintained MR4.5 with consolidation therapy, and 87 proceeded to discontinuation of nilotinib. The treatment-free remission (TFR) (MR4.5) rate at both 1 and 3 years after discontinuation of nilotinib was the same, at 60.9% (90% CI 51.6–69.7). Among 34 patients with molecular relapse, nilotinib was resumed in 33 patients; all of them attained MR4.5. There was no significant association between molecular relapse and age, sex, Sokal score, previous interferon-α exposure, duration of tyrosine kinase inhibitors treatment, or trough concentration of nilotinib. With nilotinib, it might be possible to avoid prognostic factors for TFR that exist with imatinib discontinuation. Cessation of nilotinib after two years of consolidation was safe and feasible. Trial registration UMIN000007141.

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