Efficacy and safety of switching to nilotinib in patients with CML-CP in major molecular response to imatinib

results of a multicenter phase II trial (NILSw trial)

Jun Ishikawa, Itaru Matsumura, Tatsuya Kawaguchi, Junya Kuroda, Hirohisa Nakamae, Toshihiro Miyamoto, Ken ichi Matsuoka, Hirohiko Shibayama, Masayuki Hino, Chikara Hirase, Tomohiko Kamimura, Takayuki Shimose, Koichi Akashi, Yuzuru Kanakura

Research output: Contribution to journalArticle

Abstract

We evaluated the efficacy and safety of switching to nilotinib in CML-CP patients who had achieved MMR with continuous detectable BCR-ABL1 transcript levels after long-term imatinib treatment. Patients who had achieved MMR, but not deep molecular response (DMR), after > 18 months from the initiation of imatinib received nilotinib 400 mg twice daily for up to 24 months. BCR-ABL1 transcript levels were assessed every 3 months. Thirty-eight patients with a median age of 57.5 years (range 22–76 years) were evaluated. Twenty-seven patients completed 24 months of nilotinib treatment; 11 discontinued nilotinib due to retraction of consent (three patients), loss of MMR (1), intolerance (3) or AEs (5). Twenty patients [52.6%, (90% CI 38.2–66.7%)] achieved DMR. The cumulative incidence of achieving DMR by the time of 3, 6, 9, 12, 15, 18, and 21 months was 22.9, 37.7, 47.0, 53.7, 53.7, 53.7, and 53.7%, respectively. Adverse events were consistent with those reported in other nilotinib studies. Patients experienced each of the following cardiovascular complications: atrial fibrillation (G2), chest tightness and dyspnea (G1), myocardial infarction (G2) and heart failure (G3) (n = 1 for each complication). This study indicates nilotinib achieves strong, rapid induction of DMR for patients who achieved MMR after long-term imatinib therapy.

Original languageEnglish
Pages (from-to)535-540
Number of pages6
JournalInternational journal of hematology
Volume107
Issue number5
DOIs
Publication statusPublished - May 1 2018

Fingerprint

Safety
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Imatinib Mesylate
Dyspnea
Atrial Fibrillation
Reaction Time
Thorax
Therapeutics
Heart Failure
Myocardial Infarction
Incidence

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Efficacy and safety of switching to nilotinib in patients with CML-CP in major molecular response to imatinib : results of a multicenter phase II trial (NILSw trial). / Ishikawa, Jun; Matsumura, Itaru; Kawaguchi, Tatsuya; Kuroda, Junya; Nakamae, Hirohisa; Miyamoto, Toshihiro; Matsuoka, Ken ichi; Shibayama, Hirohiko; Hino, Masayuki; Hirase, Chikara; Kamimura, Tomohiko; Shimose, Takayuki; Akashi, Koichi; Kanakura, Yuzuru.

In: International journal of hematology, Vol. 107, No. 5, 01.05.2018, p. 535-540.

Research output: Contribution to journalArticle

Ishikawa, J, Matsumura, I, Kawaguchi, T, Kuroda, J, Nakamae, H, Miyamoto, T, Matsuoka, KI, Shibayama, H, Hino, M, Hirase, C, Kamimura, T, Shimose, T, Akashi, K & Kanakura, Y 2018, 'Efficacy and safety of switching to nilotinib in patients with CML-CP in major molecular response to imatinib: results of a multicenter phase II trial (NILSw trial)', International journal of hematology, vol. 107, no. 5, pp. 535-540. https://doi.org/10.1007/s12185-018-2401-y
Ishikawa, Jun ; Matsumura, Itaru ; Kawaguchi, Tatsuya ; Kuroda, Junya ; Nakamae, Hirohisa ; Miyamoto, Toshihiro ; Matsuoka, Ken ichi ; Shibayama, Hirohiko ; Hino, Masayuki ; Hirase, Chikara ; Kamimura, Tomohiko ; Shimose, Takayuki ; Akashi, Koichi ; Kanakura, Yuzuru. / Efficacy and safety of switching to nilotinib in patients with CML-CP in major molecular response to imatinib : results of a multicenter phase II trial (NILSw trial). In: International journal of hematology. 2018 ; Vol. 107, No. 5. pp. 535-540.
@article{6ec8055e615947bcaf4de9ccb2c6a3eb,
title = "Efficacy and safety of switching to nilotinib in patients with CML-CP in major molecular response to imatinib: results of a multicenter phase II trial (NILSw trial)",
abstract = "We evaluated the efficacy and safety of switching to nilotinib in CML-CP patients who had achieved MMR with continuous detectable BCR-ABL1 transcript levels after long-term imatinib treatment. Patients who had achieved MMR, but not deep molecular response (DMR), after > 18 months from the initiation of imatinib received nilotinib 400 mg twice daily for up to 24 months. BCR-ABL1 transcript levels were assessed every 3 months. Thirty-eight patients with a median age of 57.5 years (range 22–76 years) were evaluated. Twenty-seven patients completed 24 months of nilotinib treatment; 11 discontinued nilotinib due to retraction of consent (three patients), loss of MMR (1), intolerance (3) or AEs (5). Twenty patients [52.6{\%}, (90{\%} CI 38.2–66.7{\%})] achieved DMR. The cumulative incidence of achieving DMR by the time of 3, 6, 9, 12, 15, 18, and 21 months was 22.9, 37.7, 47.0, 53.7, 53.7, 53.7, and 53.7{\%}, respectively. Adverse events were consistent with those reported in other nilotinib studies. Patients experienced each of the following cardiovascular complications: atrial fibrillation (G2), chest tightness and dyspnea (G1), myocardial infarction (G2) and heart failure (G3) (n = 1 for each complication). This study indicates nilotinib achieves strong, rapid induction of DMR for patients who achieved MMR after long-term imatinib therapy.",
author = "Jun Ishikawa and Itaru Matsumura and Tatsuya Kawaguchi and Junya Kuroda and Hirohisa Nakamae and Toshihiro Miyamoto and Matsuoka, {Ken ichi} and Hirohiko Shibayama and Masayuki Hino and Chikara Hirase and Tomohiko Kamimura and Takayuki Shimose and Koichi Akashi and Yuzuru Kanakura",
year = "2018",
month = "5",
day = "1",
doi = "10.1007/s12185-018-2401-y",
language = "English",
volume = "107",
pages = "535--540",
journal = "International Journal of Hematology",
issn = "0925-5710",
publisher = "Springer Japan",
number = "5",

}

TY - JOUR

T1 - Efficacy and safety of switching to nilotinib in patients with CML-CP in major molecular response to imatinib

T2 - results of a multicenter phase II trial (NILSw trial)

AU - Ishikawa, Jun

AU - Matsumura, Itaru

AU - Kawaguchi, Tatsuya

AU - Kuroda, Junya

AU - Nakamae, Hirohisa

AU - Miyamoto, Toshihiro

AU - Matsuoka, Ken ichi

AU - Shibayama, Hirohiko

AU - Hino, Masayuki

AU - Hirase, Chikara

AU - Kamimura, Tomohiko

AU - Shimose, Takayuki

AU - Akashi, Koichi

AU - Kanakura, Yuzuru

PY - 2018/5/1

Y1 - 2018/5/1

N2 - We evaluated the efficacy and safety of switching to nilotinib in CML-CP patients who had achieved MMR with continuous detectable BCR-ABL1 transcript levels after long-term imatinib treatment. Patients who had achieved MMR, but not deep molecular response (DMR), after > 18 months from the initiation of imatinib received nilotinib 400 mg twice daily for up to 24 months. BCR-ABL1 transcript levels were assessed every 3 months. Thirty-eight patients with a median age of 57.5 years (range 22–76 years) were evaluated. Twenty-seven patients completed 24 months of nilotinib treatment; 11 discontinued nilotinib due to retraction of consent (three patients), loss of MMR (1), intolerance (3) or AEs (5). Twenty patients [52.6%, (90% CI 38.2–66.7%)] achieved DMR. The cumulative incidence of achieving DMR by the time of 3, 6, 9, 12, 15, 18, and 21 months was 22.9, 37.7, 47.0, 53.7, 53.7, 53.7, and 53.7%, respectively. Adverse events were consistent with those reported in other nilotinib studies. Patients experienced each of the following cardiovascular complications: atrial fibrillation (G2), chest tightness and dyspnea (G1), myocardial infarction (G2) and heart failure (G3) (n = 1 for each complication). This study indicates nilotinib achieves strong, rapid induction of DMR for patients who achieved MMR after long-term imatinib therapy.

AB - We evaluated the efficacy and safety of switching to nilotinib in CML-CP patients who had achieved MMR with continuous detectable BCR-ABL1 transcript levels after long-term imatinib treatment. Patients who had achieved MMR, but not deep molecular response (DMR), after > 18 months from the initiation of imatinib received nilotinib 400 mg twice daily for up to 24 months. BCR-ABL1 transcript levels were assessed every 3 months. Thirty-eight patients with a median age of 57.5 years (range 22–76 years) were evaluated. Twenty-seven patients completed 24 months of nilotinib treatment; 11 discontinued nilotinib due to retraction of consent (three patients), loss of MMR (1), intolerance (3) or AEs (5). Twenty patients [52.6%, (90% CI 38.2–66.7%)] achieved DMR. The cumulative incidence of achieving DMR by the time of 3, 6, 9, 12, 15, 18, and 21 months was 22.9, 37.7, 47.0, 53.7, 53.7, 53.7, and 53.7%, respectively. Adverse events were consistent with those reported in other nilotinib studies. Patients experienced each of the following cardiovascular complications: atrial fibrillation (G2), chest tightness and dyspnea (G1), myocardial infarction (G2) and heart failure (G3) (n = 1 for each complication). This study indicates nilotinib achieves strong, rapid induction of DMR for patients who achieved MMR after long-term imatinib therapy.

UR - http://www.scopus.com/inward/record.url?scp=85040867577&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040867577&partnerID=8YFLogxK

U2 - 10.1007/s12185-018-2401-y

DO - 10.1007/s12185-018-2401-y

M3 - Article

VL - 107

SP - 535

EP - 540

JO - International Journal of Hematology

JF - International Journal of Hematology

SN - 0925-5710

IS - 5

ER -