Feasibility of the imatinib stop study in the Japanese clinical setting: delightedly overcome CML expert stop TKI trial (DOMEST Trial)

被引：27

作者：

Fujisawa, Shin ^{[1
]}

Ueda, Yasunori ^{[2
]}

Usuki, Kensuke ^{[3
]}

Kobayashi, Hajime ^{[4
]}

Kondo, Eisei ^{[5
]}

Doki, Noriko ^{[6
]}

Nakao, Takafumi ^{[7
]}

Kanda, Yoshinobu ^{[8
]}

Kosugi, Nobuharu ^{[9
,10
]}

Kosugi, Hiroshi ^{[10
]}

Kumagai, Takashi ^{[11
]}

Harada, Hiroshi ^{[12
]}

Shikami, Masato ^{[13
]}

Maeda, Yasuhiro ^{[14
]}

Sakura, Toru ^{[15
]}

Inokuchi, Koiti ^{[16
]}

Saito, Akio ^{[17
]}

Nawa, Yuichiro ^{[18
]}

Ogasawara, Masahiro ^{[19
]}

Nishida, Junji ^{[20
]}

Kondo, Takeshi ^{[21
]}

Yoshida, Chikashi ^{[22
]}

Kuroda, Hiroyuki ^{[23
]}

Tabe, Yoko ^{[24
]}

Maeda, Yoshinobu ^{[25
]}

Imajo, Kenji ^{[26
]}

Kojima, Kensuke ^{[27
]}

Morita, Satoshi ^{[28
]}

Komukai, Sho ^{[29
]}

Kawaguchi, Atsushi ^{[29
]}

Sakamoto, Junichi ^{[30
]}

Kimura, Shinya ^{[27
]}

机构：

[1] Yokohama City Univ, Dept Hematol, Med Ctr, Yokohama, Kanagawa, Japan

[2] Kurashiki Cent Hosp, Dept Hematol Oncol, Kurashiki, Okayama, Japan

[3] NTT Med Ctr, Dept Hematol, Tokyo, Japan

[4] Obihiro Kosei Hosp, Dept Hematol, Obihiro, Hokkaido, Japan

[5] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gen Med, Okayama, Japan

[6] Komagome Hosp, Tokyo Metropolitan Canc & Infect Dis Ctr, Div Hematol, Tokyo, Japan

[7] Osaka City Gen Hosp, Dept Hematol, Osaka, Japan

[8] Jichi Med Univ, Saitama Med Ctr, Dept Hematol, Saitama, Japan

[9] Numazu City Hosp, Dept Hematol, Numazu, Japan

[10] Ogaki Municipal Hosp, Dept Hematol, Ogaki, Japan

[11] Ome Municipal Gen Hosp, Dept Hematol, Ome, Japan

[12] Showa Univ, Dept Med, Fujigaoka Hosp, Div Hematol, Yokohama, Kanagawa, Japan

[13] Daiyukai Gen Hosp, Dept Hematol, Ichinomiya, Japan

[14] Natl Hosp Org Osaka Minami Med Ctr, Dept Hematol, Osaka, Japan

[15] Saiseikai Maebashi Hosp, Dept Hematol, Maebashi, Gunma, Japan

[16] Nippon Med Sch, Dept Hematol, Tokyo, Japan

[17] Fujioka Gen Hosp, Dept Hematol, Fujioka, Japan

[18] Ehime Prefectural Cent Hosp, Dept Hematol, Matsuyama, Ehime, Japan

[19] Sapporo Hokuyu Hosp, Dept Hematol, Sapporo, Hokkaido, Japan

[20] Jichi Med Univ, Saitama Med Ctr, Div Hematol, Saitama, Japan

[21] Hokkaido Univ Hosp, Dept Hematol, Sapporo, Hokkaido, Japan

[22] Natl Hosp Org Mito Med Ctr, Dept Hematol, Mito, Ibaraki, Japan

[23] Steel Muroran Mem Hosp, Dept Gastroenterol & Hematol Clin Oncol, Muroran, Hokkaido, Japan

[24] Juntendo Univ, Dept Next Generat Hematol Lab Med, Fac Med, Tokyo, Japan

[25] Okayama Univ Hosp, Dept Hematol & Oncol, Okayama, Japan

[26] Okayama Municipal Hosp, Dept Internal Med, Okayama, Japan

[27] Saga Univ, Div Hematol Resp Med & Oncol, Dept Internal Med, Fac Med, Saga, Japan

[28] Kyoto Univ, Dept Biomed Stat & Bioinformat, Grad Sch Med, Kyoto, Japan

[29] Osaka Univ, Grad Sch Med, Div Biomed Stat, Dept Integrated Med, Osaka, Japan

[30] Tokai Cent Hosp, Kakamigahara, Japan

来源：

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY | 2019年 / 24卷 / 04期

关键词：

Chronic myelogenous leukemia; Treatment-free remission; Imatinib; Deep molecular response; Molecular recurrence-free survival; CHRONIC MYELOID-LEUKEMIA; TREATMENT-FREE REMISSION; MOLECULAR RESPONSE; DISCONTINUATION; DASATINIB; THERAPY; CELLS; RELAPSE; LONGER;

D O I：

10.1007/s10147-018-1368-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：445 / 453

页数：9

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