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

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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)1-6
Number of pages6
JournalInternational Journal of Hematology
DOIs
Publication statusAccepted/In press - Jan 23 2018

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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

Keywords

  • Chronic myelogeneous leukemia
  • Deep molecular response
  • Imatinib
  • Major molecular response
  • Nilotinib

ASJC Scopus subject areas

  • 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, 23.01.2018, p. 1-6.

Research output: Contribution to journalArticle

Ishikawa, J, Matsumura, I, Kawaguchi, T, Kuroda, J, Nakamae, H, Miyamoto, T, Matsuoka, K, 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, pp. 1-6. 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 ; pp. 1-6.
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