Page 95 - 2018_11-Haematologica-web

Chronic Myeloid Leukemia
Treatment-free remission after two-year consolidation therapy with nilotinib
in patients with chronic myeloid leukemia: STAT2 trial in Japan
Naoto Takahashi,1 Kaichi Nishiwaki,2 Chiaki Nakaseko,3,4 Nobuyuki Aotsuka,5 Koji Sano,2 Chikako Ohwada,4 Jun Kuroki,6 Hideo Kimura,7
Michihide Tokuhira,8 Kinuko Mitani,9 Kazuhisa Fujikawa,10 Osamu Iwase,11 Kohshi Ohishi,12 Fumihiko Kimura,13 Tetsuya Fukuda,14,15 Sakae Tanosaki,16 Saori Takahashi,17 Yoshihiro Kameoka,17 Hiroyoshi Nishikawa,18
Ferrata Storti Foundation
Hisashi Wakita5,19 and the STAT study group
Haematologica 2018 Volume 103(11):1835-1842
1Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine; 2Department of Oncology and Hematology, Jikei University Kashiwa Hospital; 3 Department of Hematology, International University of Health and Welfare School of Medicine, Narita; 4Department of Hematology, Chiba University Hospital; 5Department of Hematology and Oncology, Japanese Red Cross Narita Hospital; 6Department of Internal Medicine, Yuri General Hospital, Yurihonjo; 7Department of Hematology, Northern Fukushima Medical Center, Date; 8Department of Hematology, Saitama Medical Center, Saitama Medical University, Kawagoe; 9Department of Hematology and Oncology, Dokkyo Medical University, Tochigi; 10Department of Hematology, Chibaken Saiseikai Narashino Hospital; 11Department of Hematology, Tokyo Medical University Hachioji Medical Center; 12Transfusion Medicine and Cell Therapy, Mie University Hospital, Tsu; 13Division of Hematology, National Defense Medical College, Tokorozawa; 14Department of Hematology, Tokyo Medical and Dental University Hospital; 15Department of Hematology, Tottori University Hospital, Yonago; 16Department of Hematology, The Fraternity Memorial Hospital, Tokyo; 17Clinical Research Promotion and Support Center, Akita University Hospital; 18Division of Cancer Immunology, Research Institute / Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Tokyo/Kashiwa and 19Japanese Red Cross Chiba Blood Center, Funabashi, Japan
ABSTRACT
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 con- firmed 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 achiev- ing 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 sur- vival, 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
Correspondence:
naotot@doc.med.akita-u.ac.jp
Received: April 4, 2018. Accepted: June 28, 2018. Pre-published: July 5, 2018.
doi:10.3324/haematol.2018.194894
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/11/1835
©2018 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
haematologica | 2018; 103(11)
1835
ARTICLE