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

Shin Fujisawa, Yasunori Ueda, Kensuke Usuki, Hajime Kobayashi, Eisei Kondo, Noriko Doki, Takafumi Nakao, Yoshinobu Kanda, Nobuharu Kosugi, Hiroshi Kosugi, Takashi Kumagai, Hiroshi Harada, Masato Shikami, Yasuhiro Maeda, Toru Sakura, Koiti Inokuchi, Akio Saito, Yuichiro Nawa, Masahiro Ogasawara, Junji NishidaTakeshi Kondo, Chikashi Yoshida, Hiroyuki Kuroda, Yoko Tabe, Yoshinobu Maeda, Kenji Imajo, Kensuke Kojima, Satoshi Morita, Sho Komukai, Atsushi Kawaguchi, Junichi Sakamoto, Shinya Kimura

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
JournalInternational Journal of Clinical Oncology
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Recurrence
Therapeutics
Imatinib Mesylate
Multivariate Analysis
Survival Rate
Safety
Polymerase Chain Reaction

Keywords

  • Chronic myelogenous leukemia
  • Deep molecular response
  • Imatinib
  • Molecular recurrence-free survival
  • Treatment-free remission

ASJC Scopus subject areas

  • Surgery
  • Hematology
  • Oncology

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Feasibility of the imatinib stop study in the Japanese clinical setting : delightedly overcome CML expert stop TKI trial (DOMEST Trial). / Fujisawa, Shin; Ueda, Yasunori; Usuki, Kensuke; Kobayashi, Hajime; Kondo, Eisei; Doki, Noriko; Nakao, Takafumi; Kanda, Yoshinobu; Kosugi, Nobuharu; Kosugi, Hiroshi; Kumagai, Takashi; Harada, Hiroshi; Shikami, Masato; Maeda, Yasuhiro; Sakura, Toru; Inokuchi, Koiti; Saito, Akio; Nawa, Yuichiro; Ogasawara, Masahiro; Nishida, Junji; Kondo, Takeshi; Yoshida, Chikashi; Kuroda, Hiroyuki; Tabe, Yoko; Maeda, Yoshinobu; Imajo, Kenji; Kojima, Kensuke; Morita, Satoshi; Komukai, Sho; Kawaguchi, Atsushi; Sakamoto, Junichi; Kimura, Shinya.

In: International Journal of Clinical Oncology, 01.01.2018.

Research output: Contribution to journalArticle

Fujisawa, S, Ueda, Y, Usuki, K, Kobayashi, H, Kondo, E, Doki, N, Nakao, T, Kanda, Y, Kosugi, N, Kosugi, H, Kumagai, T, Harada, H, Shikami, M, Maeda, Y, Sakura, T, Inokuchi, K, Saito, A, Nawa, Y, Ogasawara, M, Nishida, J, Kondo, T, Yoshida, C, Kuroda, H, Tabe, Y, Maeda, Y, Imajo, K, Kojima, K, Morita, S, Komukai, S, Kawaguchi, A, Sakamoto, J & Kimura, S 2018, 'Feasibility of the imatinib stop study in the Japanese clinical setting: delightedly overcome CML expert stop TKI trial (DOMEST Trial)', International Journal of Clinical Oncology. https://doi.org/10.1007/s10147-018-1368-2
Fujisawa, Shin ; Ueda, Yasunori ; Usuki, Kensuke ; Kobayashi, Hajime ; Kondo, Eisei ; Doki, Noriko ; Nakao, Takafumi ; Kanda, Yoshinobu ; Kosugi, Nobuharu ; Kosugi, Hiroshi ; Kumagai, Takashi ; Harada, Hiroshi ; Shikami, Masato ; Maeda, Yasuhiro ; Sakura, Toru ; Inokuchi, Koiti ; Saito, Akio ; Nawa, Yuichiro ; Ogasawara, Masahiro ; Nishida, Junji ; Kondo, Takeshi ; Yoshida, Chikashi ; Kuroda, Hiroyuki ; Tabe, Yoko ; Maeda, Yoshinobu ; Imajo, Kenji ; Kojima, Kensuke ; Morita, Satoshi ; Komukai, Sho ; Kawaguchi, Atsushi ; Sakamoto, Junichi ; Kimura, Shinya. / Feasibility of the imatinib stop study in the Japanese clinical setting : delightedly overcome CML expert stop TKI trial (DOMEST Trial). In: International Journal of Clinical Oncology. 2018.
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abstract = "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.",
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author = "Shin Fujisawa and Yasunori Ueda and Kensuke Usuki and Hajime Kobayashi and Eisei Kondo and Noriko Doki and Takafumi Nakao and Yoshinobu Kanda and Nobuharu Kosugi and Hiroshi Kosugi and Takashi Kumagai and Hiroshi Harada and Masato Shikami and Yasuhiro Maeda and Toru Sakura and Koiti Inokuchi and Akio Saito and Yuichiro Nawa and Masahiro Ogasawara and Junji Nishida and Takeshi Kondo and Chikashi Yoshida and Hiroyuki Kuroda and Yoko Tabe and Yoshinobu Maeda and Kenji Imajo and Kensuke Kojima and Satoshi Morita and Sho Komukai and Atsushi Kawaguchi and Junichi Sakamoto and Shinya Kimura",
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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

PY - 2018/1/1

Y1 - 2018/1/1

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

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