Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib: SENSOR final results and BIM polymorphism substudy

Koichi Miyamura, Toshihiro Miyamoto, Mitsune Tanimoto, Kazuhito Yamamoto, Shinya Kimura, Tatsuya Kawaguchi, Itaru Matsumura, Tomoko Hata, Hisashi Tsurumi, Shigeki Saito, Masayuki Hino, Seiji Tadokoro, Kuniaki Meguro, Hideo Hyodo, Masahide Yamamoto, Kohmei Kubo, Junichi Tsukada, Midori Kondo, Makoto Aoki, Hikaru OkadaMasamitsu Yanada, Kazuma Ohyashiki, Masafumi Taniwaki

Research output: Contribution to journalArticle

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Abstract

Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after ≥18 months of frontline imatinib received nilotinib 400 mg twice daily for 24 months. MR, BCR-ABL1 mutations/variants, and BIM polymorphisms were evaluated in a central laboratory. Primary endpoint was the MMR rate at 12 months (null hypothesis of 40%). Of 45 patients (median exposure, 22.08 months), 39 completed the study and six discontinued. At 12 and 24 months, 51.1% (95% CI, 35.8%–66.3%) and 66.7% (95% CI, 51.0%–80.0%) achieved MMR, respectively. Cumulative MMR incidence by 24 months was 75.6%. Of 40 patients analyzed, 10 of 12 (83.3%) with and 17 of 28 (60.7%) without BIM polymorphisms achieved MMR at 24 months. The safety profile was manageable with dose reductions and interruptions. Nilotinib provided clinical benefit for patients with suboptimal response to imatinib, and BIM polymorphisms did not influence MMR achievement. ClinicalTrials.gov: NCT01043874.

Original languageEnglish
Pages (from-to)11-18
Number of pages8
JournalLeukemia Research
Volume51
DOIs
Publication statusPublished - Dec 1 2016

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Leukemia, Myeloid, Chronic Phase
Safety
Cytogenetics
Multicenter Studies
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Imatinib Mesylate
Mutation
Incidence

Keywords

  • BIM polymorphism
  • Chronic myeloid leukemia
  • Japanese
  • Molecular response
  • Nilotinib
  • Suboptimal response

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib : SENSOR final results and BIM polymorphism substudy. / Miyamura, Koichi; Miyamoto, Toshihiro; Tanimoto, Mitsune; Yamamoto, Kazuhito; Kimura, Shinya; Kawaguchi, Tatsuya; Matsumura, Itaru; Hata, Tomoko; Tsurumi, Hisashi; Saito, Shigeki; Hino, Masayuki; Tadokoro, Seiji; Meguro, Kuniaki; Hyodo, Hideo; Yamamoto, Masahide; Kubo, Kohmei; Tsukada, Junichi; Kondo, Midori; Aoki, Makoto; Okada, Hikaru; Yanada, Masamitsu; Ohyashiki, Kazuma; Taniwaki, Masafumi.

In: Leukemia Research, Vol. 51, 01.12.2016, p. 11-18.

Research output: Contribution to journalArticle

Miyamura, K, Miyamoto, T, Tanimoto, M, Yamamoto, K, Kimura, S, Kawaguchi, T, Matsumura, I, Hata, T, Tsurumi, H, Saito, S, Hino, M, Tadokoro, S, Meguro, K, Hyodo, H, Yamamoto, M, Kubo, K, Tsukada, J, Kondo, M, Aoki, M, Okada, H, Yanada, M, Ohyashiki, K & Taniwaki, M 2016, 'Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib: SENSOR final results and BIM polymorphism substudy', Leukemia Research, vol. 51, pp. 11-18. https://doi.org/10.1016/j.leukres.2016.09.009
Miyamura, Koichi ; Miyamoto, Toshihiro ; Tanimoto, Mitsune ; Yamamoto, Kazuhito ; Kimura, Shinya ; Kawaguchi, Tatsuya ; Matsumura, Itaru ; Hata, Tomoko ; Tsurumi, Hisashi ; Saito, Shigeki ; Hino, Masayuki ; Tadokoro, Seiji ; Meguro, Kuniaki ; Hyodo, Hideo ; Yamamoto, Masahide ; Kubo, Kohmei ; Tsukada, Junichi ; Kondo, Midori ; Aoki, Makoto ; Okada, Hikaru ; Yanada, Masamitsu ; Ohyashiki, Kazuma ; Taniwaki, Masafumi. / Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib : SENSOR final results and BIM polymorphism substudy. In: Leukemia Research. 2016 ; Vol. 51. pp. 11-18.
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AU - Tanimoto, Mitsune

AU - Yamamoto, Kazuhito

AU - Kimura, Shinya

AU - Kawaguchi, Tatsuya

AU - Matsumura, Itaru

AU - Hata, Tomoko

AU - Tsurumi, Hisashi

AU - Saito, Shigeki

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AU - Meguro, Kuniaki

AU - Hyodo, Hideo

AU - Yamamoto, Masahide

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AU - Kondo, Midori

AU - Aoki, Makoto

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AU - Ohyashiki, Kazuma

AU - Taniwaki, Masafumi

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