TY - JOUR
T1 - Feasibility of the imatinib stop study in the Japanese clinical setting
T2 - delightedly overcome CML expert stop TKI trial (DOMEST Trial)
AU - Fujisawa, Shin
AU - Ueda, Yasunori
AU - Usuki, Kensuke
AU - Kobayashi, Hajime
AU - Kondo, Eisei
AU - Doki, Noriko
AU - Nakao, Takafumi
AU - Kanda, Yoshinobu
AU - Kosugi, Nobuharu
AU - Kosugi, Hiroshi
AU - Kumagai, Takashi
AU - Harada, Hiroshi
AU - Shikami, Masato
AU - Maeda, Yasuhiro
AU - Sakura, Toru
AU - Inokuchi, Koiti
AU - Saito, Akio
AU - Nawa, Yuichiro
AU - Ogasawara, Masahiro
AU - Nishida, Junji
AU - Kondo, Takeshi
AU - Yoshida, Chikashi
AU - Kuroda, Hiroyuki
AU - Tabe, Yoko
AU - Maeda, Yoshinobu
AU - Imajo, Kenji
AU - Kojima, Kensuke
AU - Morita, Satoshi
AU - Komukai, Sho
AU - Kawaguchi, Atsushi
AU - Sakamoto, Junichi
AU - Kimura, Shinya
N1 - Funding Information:
This study was supported by the Epidemiological and Clinical Research Information Network (ECRIN). We thank Yumi Miyashita at ECRIN for collecting the data and Yoshinori Yamamoto at BML for measuring the data.
Funding Information:
Acknowledgements This study was supported by the Epidemiological and Clinical Research Information Network (ECRIN). We thank Yumi Miyashita at ECRIN for collecting the data and Yoshinori Yamamoto at BML for measuring the data.
Funding Information:
Conflict of interest S. Fujisawa has received honoraria from Bristol-Myers Squibb, Novartis, Pfizer, and Otsuka Pharmaceuticals and research funding form Pfizer and Novartis. K. Usuki has received honoraria from MSD K.K, Sumitomo Dainippon Pharma, Pfizer Japan, Celgene Corporation, Novartis, Ono Pharmaceutical, Takeda Pharmaceuticals, Chugai Pharmaceutical, Nippon Shinyaku, and Mochida Pharmaceutical and research funding from MSD K.K, Sumitomo Dainippon Pharma, Pfizer Japan, Celgene Corporation, As-tellas Pharma, Otsuka, Kyowa Kirin, Glaxo Smithkline K.K, Sanofi K.K, Shire Japan, Symbio Pharmaceuticals Limited, Daiichi Sankyo, Boehringer-Ingelheim Japan, and Janssen Pharmaceutical K,K. Y.
Publisher Copyright:
© 2018, The Author(s).
PY - 2019/4/15
Y1 - 2019/4/15
N2 - Background: Treatment-free remission (TFR), the ability to maintain a molecular response (MR), occurs in approximately 50% of patients with chronic myelogenous leukemia (CML) treated with tyrosine kinase inhibitors (TKIs). Methods: A multicenter phase 2 trial (Delightedly Overcome CML Expert Stop TKI Trial: DOMEST Trial) was conducted to test the safety and efficacy of discontinuing imatinib. Patients with CML with a sustained MR of 4.0 or MR4.0-equivalent for at least 2 years and confirmed MR4.0 at the beginning of the study were enrolled. In the TFR phase, the international scale (IS) was regularly monitored by IS-PCR testing. Molecular recurrence was defined as the loss of MR4.0. Recurrent patients were immediately treated with dasatinib or other TKIs including imatinib. Results: Of 110 enrolled patients, 99 were evaluable. The median time from diagnosis to discontinuation of imatinib was 103 months, and the median duration of imatinib therapy was 100 months. Molecular recurrence-free survival rates were 69.6%, 68.6% and 64.3% at 6, 12, and 24 months, respectively. After discontinuation of imatinib therapy, 26 patients showed molecular recurrence, and 25 re-achieved deep MR after dasatinib treatment. Molecular response MR4.0 was achieved in 23 patients within 6 months and 25 patients within 12 months. Multivariate analysis revealed that a longer time from diagnosis to discontinuation of imatinib therapy (p = 0.0002) and long duration of imatinib therapy (p = 0.0029) predicted a favorable prognosis. Conclusions: This DOMEST Trial showed the feasibility of TKI discontinuation in a Japanese clinical setting.
AB - Background: Treatment-free remission (TFR), the ability to maintain a molecular response (MR), occurs in approximately 50% of patients with chronic myelogenous leukemia (CML) treated with tyrosine kinase inhibitors (TKIs). Methods: A multicenter phase 2 trial (Delightedly Overcome CML Expert Stop TKI Trial: DOMEST Trial) was conducted to test the safety and efficacy of discontinuing imatinib. Patients with CML with a sustained MR of 4.0 or MR4.0-equivalent for at least 2 years and confirmed MR4.0 at the beginning of the study were enrolled. In the TFR phase, the international scale (IS) was regularly monitored by IS-PCR testing. Molecular recurrence was defined as the loss of MR4.0. Recurrent patients were immediately treated with dasatinib or other TKIs including imatinib. Results: Of 110 enrolled patients, 99 were evaluable. The median time from diagnosis to discontinuation of imatinib was 103 months, and the median duration of imatinib therapy was 100 months. Molecular recurrence-free survival rates were 69.6%, 68.6% and 64.3% at 6, 12, and 24 months, respectively. After discontinuation of imatinib therapy, 26 patients showed molecular recurrence, and 25 re-achieved deep MR after dasatinib treatment. Molecular response MR4.0 was achieved in 23 patients within 6 months and 25 patients within 12 months. Multivariate analysis revealed that a longer time from diagnosis to discontinuation of imatinib therapy (p = 0.0002) and long duration of imatinib therapy (p = 0.0029) predicted a favorable prognosis. Conclusions: This DOMEST Trial showed the feasibility of TKI discontinuation in a Japanese clinical setting.
KW - Chronic myelogenous leukemia
KW - Deep molecular response
KW - Imatinib
KW - Molecular recurrence-free survival
KW - Treatment-free remission
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U2 - 10.1007/s10147-018-1368-2
DO - 10.1007/s10147-018-1368-2
M3 - Article
C2 - 30421023
AN - SCOPUS:85056474510
SN - 1341-9625
VL - 24
SP - 445
EP - 453
JO - International Journal of Clinical Oncology
JF - International Journal of Clinical Oncology
IS - 4
ER -