Treatment-free remission after two-year consolidation therapy with nilotinib in patients with chronic myeloid leukemia: STAT2 trial in Japan
Naoto Takahashi,
Kaichi Nishiwaki,
Chiaki Nakaseko,
Nobuyuki Aotsuka,
Koji Sano,
Chikako Ohwada,
Jun Kuroki,
Hideo Kimura,
Michihide Tokuhira,
Kinuko Mitani,
Kazuhisa Fujikawa,
Osamu Iwase,
Kohshi Ohishi,
Fumihiko Kimura,
Tetsuya Fukuda,
Sakae Tanosaki,
Saori Takahashi,
Yoshihiro Kameoka,
Hiroyoshi Nishikawa,
Hisashi Wakita
Affiliations
Naoto Takahashi
Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine
Kaichi Nishiwaki
Department of Oncology and Hematology, Jikei University Kashiwa Hospital
Chiaki Nakaseko
Department of Hematology, International University of Health and Welfare School of Medicine, Narita;Department of Hematology, Chiba University Hospital
Nobuyuki Aotsuka
Department of Hematology and Oncology, Japanese Red Cross Narita Hospital
Koji Sano
Department of Oncology and Hematology, Jikei University Kashiwa Hospital
Chikako Ohwada
Department of Hematology, Chiba University Hospital
Jun Kuroki
Department of Internal Medicine, Yuri General Hospital, Yurihonjo
Hideo Kimura
Department of Hematology, Northern Fukushima Medical Center, Date
Michihide Tokuhira
Department of Hematology, Saitama Medical Center, Saitama Medical University, Kawagoe
Kinuko Mitani
Department of Hematology and Oncology, Dokkyo Medical University, Tochigi
Kazuhisa Fujikawa
Department of Hematology, Chibaken Saiseikai Narashino Hospital
Osamu Iwase
Department of Hematology, Tokyo Medical University Hachioji Medical Center
Kohshi Ohishi
Transfusion Medicine and Cell Therapy, Mie University Hospital, Tsu
Fumihiko Kimura
Division of Hematology, National Defense Medical College, Tokorozawa
Tetsuya Fukuda
Department of Hematology, Tokyo Medical and Dental University Hospital;Department of Hematology, Tottori University Hospital, Yonago
Sakae Tanosaki
Department of Hematology, The Fraternity Memorial Hospital, Tokyo
Saori Takahashi
Clinical Research Promotion and Support Center, Akita University Hospital
Yoshihiro Kameoka
Clinical Research Promotion and Support Center, Akita University Hospital
Hiroyoshi Nishikawa
Division of Cancer Immunology, Research Institute / Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Tokyo/Kashiwa
Hisashi Wakita
Department of Hematology and Oncology, Japanese Red Cross Narita Hospital;Japanese Red Cross Chiba Blood Center, Funabashi, Japan
The purpose of this trial was to evaluate the efficacy of 2-year consolidation therapy with nilotinib, at a dose of 300 mg twice daily, for achieving treatment-free remission in chronic myeloid leukemia patients with a deep molecular response (BCR-ABL1IS ≤0.0032%). Successful treatment-free remission was defined as no confirmed loss of deep molecular response. We recruited 96 Japanese patients, of whom 78 sustained a deep molecular response during the consolidation phase and were therefore eligible to discontinue nilotinib in the treatment-free remission phase; of these, 53 patients (67.9%; 95% confidence interval: 56.4–78.1%) remained free from molecular recurrence in the first 12 months. The estimated 3-year treatment-free survival was 62.8%. Nilotinib was readministered to all patients (n=29) who experienced a molecular recurrence during the treatment-free remission phase. After restarting treatment, rapid deep molecular response returned in 25 patients (86.2%), with 50% of patients achieving a deep molecular response within 3.5 months. Tyrosine kinase inhibitor withdrawal syndrome was reported in 11/78 patients during the early treatment-free remission phase. The treatment-free survival curve was significantly better in patients with undetectable molecular residual disease than in patients without (3-year treatment-free survival, 75.6 versus 48.6%, respectively; P=0.0126 by the log-rank test). There were no significant differences in treatment-free survival between subgroups based on tyrosine kinase inhibitor treatment before the nilotinib consolidation phase, tyrosine kinase inhibitor-withdrawal syndrome, or absolute number of natural killer cells. The results of this study indicate that it is safe and feasible to stop tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia who have achieved a sustained deep molecular response with 2 years of treatment with nilotinib. This study was registered with UMIN-CTR (UMIN000005904).
