title: 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.
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 400mg 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.
authors: Department of Hematology, Japanese Red Cross Nagoya Daiichi Hospital, 3-35 Michisita-cho, Nakamura-ku, Nagoya 453-8511, Japan. Electronic address: miyamu@nagoya-1st.jrc.or.jp.
authors: Koichi
authors: K
authors: Miyamura
authors: Medicine and Biosystemic Science, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: toshmiya@intmed1.med.kyushu-u.ac.jp.
authors: Toshihiro
authors: T
authors: Miyamoto
authors: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Okayama City, Okayama 700-8558, Japan. Electronic address: tanimoto@md.okayama-u.ac.jp.
authors: Mitsune
authors: M
authors: Tanimoto
authors: Department of Clinical Research and Department of Hematology and Cell Therapy, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. Electronic address: kyamamoto@aichi-cc.jp.
authors: Kazuhito
authors: K
authors: Yamamoto
authors: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan. Electronic address: shkimu@cc.saga-u.ac.jp.
authors: Shinya
authors: S
authors: Kimura
authors: Department of Hematology and Infectious Diseases, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. Electronic address: tatsu@kumamoto-u.ac.jp.
authors: Tatsuya
authors: T
authors: Kawaguchi
authors: Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osakasayama City, Osaka 589-8511, Japan. Electronic address: i.matsu@med.kindai.ac.jp.
authors: Itaru
authors: I
authors: Matsumura
authors: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Electronic address: hatatmk@nagasaki-u.ac.jp.
authors: Tomoko
authors: T
authors: Hata
authors: First Department of Internal Medicine, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. Electronic address: htsuru@gifu-u.ac.jp.
authors: Hisashi
authors: H
authors: Tsurumi
authors: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: shigekix19771124@hotmail.com.
authors: Shigeki
authors: S
authors: Saito
authors: Department of Hematology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. Electronic address: hinom@med.osaka-cu.ac.jp.
authors: Masayuki
authors: M
authors: Hino
authors: Department of Hematology and Oncology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. Electronic address: tadokoro@hp-blood.med.osaka-u.ac.jp.
authors: Seiji
authors: S
authors: Tadokoro
authors: Department of Hematology, Sendai Medical Center, National Hospital Organization, 2-8-8 Miyagino, Miyagino-ku, Sendai 983-8520, Japan. Electronic address: kumegu@snh.go.jp.
authors: Kuniaki
authors: K
authors: Meguro
authors: Division of Clinical Research, Department of Haematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan; Department of Internal Medicine, Amagasaki Chuo Hospital, 1-12-1 Shioe Amagasaki, Hyogo 661-0976, Japan. Electronic address: mari0105@ab.auone-net.jp.
authors: Hideo
authors: H
authors: Hyodo
authors: Department of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: hide.hema@tmd.ac.jp.
authors: Masahide
authors: M
authors: Yamamoto
authors: Department of Hematology, Aomori Prefectural Central Hospital, 2-1-1 Higashi-Tsukurimichi, Aomori-shi, Aomori 030-8553, Japan. Electronic address: komei.kubo@nifty.com.
authors: Kohmei
authors: K
authors: Kubo
authors: Hematology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. Electronic address: jtsukada@med.uoeh-u.ac.jp.
authors: Junichi
authors: J
authors: Tsukada
authors: Oncology Development & Medical Affairs Department, Novartis Pharma K.K., 1-23-1 Toranomon, Minato-ku, Tokyo 105-6333, Japan. Electronic address: midori.kondo@novartis.com.
authors: Midori
authors: M
authors: Kondo
authors: Integrated Science and Operations Department, Novartis Pharma K.K., 1-23-1 Toranomon, Minato-ku, Tokyo 105-6333, Japan. Electronic address: makoto-1.aoki@novartis.com.
authors: Makoto
authors: M
authors: Aoki
authors: Oncology Development & Medical Affairs Department, Novartis Pharma K.K., 1-23-1 Toranomon, Minato-ku, Tokyo 105-6333, Japan. Electronic address: hikaru.okada@novartis.com.
authors: Hikaru
authors: H
authors: Okada
authors: Department of Hematology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Japan. Electronic address: myanada@fujita-hu.ac.jp.
authors: Masamitsu
authors: M
authors: Yanada
authors: Department of Hematology, Tokyo Medical University, 6-7-1 Nishishinjuku, Tokyo 160-0023, Japan. Electronic address: ohyashik@rr.iij4u.or.jp.
authors: Kazuma
authors: K
authors: Ohyashiki
authors: Division of Haematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan. Electronic address: taniwaki@koto.kpu-m.ac.jp.
authors: Masafumi
authors: M
authors: Taniwaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D057915:Drug Substitution / Q000379:methods*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib
keywords: BIM polymorphism; Chronic myeloid leukemia; Japanese; Molecular response; Nilotinib; Suboptimal response