Journal Article Final 3-year Results of the Dasatinib Discontinuation Trial in Patients With Chronic Myeloid Leukemia Who Received Dasatinib as a Second-line Treatment

Okada, Masaya  ,  Imagawa, Jun  ,  Tanaka, Hideo  ,  Nakamae, Hirohisa  ,  Hino, Masayuki  ,  Murai, Kazunori  ,  Ishida, Yoji  ,  Kumagai, Takashi  ,  Sato, Seiichi  ,  Ohashi, Kazuteru  ,  Sakamaki, Hisashi  ,  Wakita, Hisashi  ,  Uoshima, Nobuhiko  ,  Nakagawa, Yasunori  ,  Minami, Yosuke  ,  Ogasawara, Masahiro  ,  Takeoka, Tomoharu  ,  Akasaka, Hiroshi  ,  Utsumi, Takahiko  ,  Uike, Naokuni  ,  Sato, Tsutomu  ,  Ando, Sachiko  ,  Usuki, Kensuke  ,  Mizuta, Syuichi  ,  Hashino, Satoshi  ,  Nomura, Tetsuhiko  ,  Shikami, Masato  ,  Fukutani, Hisashi  ,  Ohe, Yokiko  ,  Kosugi, Hiroshi  ,  Shibayama, Hirohiko  ,  Maeda, Yasuhiro  ,  Fukushima, Toshihiro  ,  Yamazaki, Hirohito  ,  Tsubaki, Kazuo  ,  Kukita, Toshimasa  ,  Adachi, Yoko  ,  Nataduka, Toshiki  ,  Sakoda, Hiroto  ,  Yokoyama, Hisayuki  ,  Okamoto, Takahiro  ,  Shirasugi, Yukari  ,  Onishi, Yasushi  ,  Nohgawa, Masaharu  ,  Yoshihara, Satoshi  ,  Morita, Satoshi  ,  Sakamoto, Junichi  ,  Kimura, Shinya  ,  DADI Trial Group, Japan

18 ( 5 )  , pp.353 - 360.e1 , 2018-05 , Elsevier BV
ISSN:2152-2650
Description
Introduction: We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. Patients and Methods: The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for ≥ 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment-free remission (TFR) were analyzed. Results: The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low γδ+ T-cell and CD4+ regulatory T-cell (CD25+CD127low) counts before discontinuation correlated significantly with successful therapy discontinuation. Conclusion: These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR.
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http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/230949/1/j.clml.2018.03.004.pdf

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