Imagawa Jun, Tanaka Hideo, Okada Masaya, 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, Morita Satoshi, Sakamoto Junichi, Kimura Shinya
Department of Haematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Department of Haematology, Hiroshima City Asa Hospital, Hiroshima, Japan.
Lancet Haematol. 2015 Dec;2(12):e528-35. doi: 10.1016/S2352-3026(15)00196-9. Epub 2015 Nov 10.
First-line imatinib treatment can be successfully discontinued in patients with chronic myeloid leukaemia after deep molecular response has been sustained for at least 2 years. We investigated the safety and efficacy of discontinuing second-line or subsequent dasatinib after at least 1 year of deep molecular response.
The Dasatinib Discontinuation trial was a prospective multicentre trial done in Japan. Eligible patients taking dasatinib and with confirmed stable deep molecular response were enrolled between April 1, 2011, and March 31, 2012. All patients received dasatinib consolidation therapy for at least 1 year. In those with sustained deep molecular response, dasatinib was discontinued. Patients were followed up every month in year 1 (clinical cutoff), every 3 months in year 2, and every 6 months in year 3 for deep molecular response and immunological profiles. The primary endpoint was the proportion of patients with treatment-free remission at 6 months after discontinuation. Molecular relapse was defined as loss of deep molecular response at any assessment. This study is registered, number UMIN000005130.
88 patients were enrolled in the consolidation phase, 24 were excluded from the discontinuation phase due to fluctuations in BCR-ABL1 transcript levels. One patient was excluded because of positive expression of major and minor BCR-ABL1 transcripts in chronic myeloid leukaemia cells and the detection of minor BCR-ABL1 transcripts during consolidation. Thus, 63 patients discontinued dasatinib treatment. The 25 patients who were excluded from discontinuation continued to receive dasatinib and none showed disease progression. Median follow-up was 20.0 months (IQR 16.5-24.0). Of the 63 patients who discontinued and were not excluded, 30 patients maintained deep molecular response while 33 patients had molecular relapses, all within the first 7 months after discontinuation. The estimated overall treatment-free remission was 49% (95% CI 36-61) at 6 months. No severe treatment-related toxic effects were seen. Treatment was restarted in the 33 patients with relapse; rapid molecular responses were seen in all 33 patients, of whom 29 (88%) regained deep molecular response within 3 months, as did the remaining four by 6 months.
Dasatinib discontinuation after sustained deep molecular response for more than 1 year is feasible.
Epidemiological and Clinical Research Information Network (ECRIN).
在慢性髓性白血病患者中，一线伊马替尼治疗在深度分子反应持续至少2年后可成功停药。我们研究了在深度分子反应至少1年后停用二线或后续达沙替尼的安全性和疗效。
达沙替尼停药试验是在日本进行的一项前瞻性多中心试验。2011年4月1日至2012年3月31日期间，纳入了服用达沙替尼且确诊为稳定深度分子反应的符合条件患者。所有患者接受达沙替尼巩固治疗至少1年。在深度分子反应持续的患者中，停用达沙替尼。第1年（临床截止）每月对患者进行随访，第2年每3个月随访一次，第3年每6个月随访一次，以评估深度分子反应和免疫谱。主要终点是停药后6个月时无治疗缓解的患者比例。分子复发定义为在任何评估中深度分子反应丧失。本研究已注册，注册号为UMIN000005130。
88例患者进入巩固期，24例因BCR-ABL1转录水平波动被排除在停药期。1例患者因慢性髓性白血病细胞中主要和次要BCR-ABL1转录本阳性表达以及巩固期检测到次要BCR-ABL1转录本而被排除。因此，63例患者停用达沙替尼治疗。被排除在停药之外的25例患者继续接受达沙替尼治疗，均未出现疾病进展。中位随访时间为20.0个月（四分位间距16.5 - 24.0）。在63例停药且未被排除的患者中，30例患者维持深度分子反应，33例患者出现分子复发，均在停药后的前7个月内。停药后6个月时，估计总体无治疗缓解率为49%（95%CI 36 - 61）。未观察到严重的治疗相关毒性作用。33例复发患者重新开始治疗；所有33例患者均出现快速分子反应，其中29例（88%）在3个月内恢复深度分子反应，其余4例在6个月内恢复。
深度分子反应持续超过1年后停用达沙替尼是可行的。
流行病学与临床研究信息网络（ECRIN）。
