Lee Sung-Eun, Choi Soo Young, Song Hye-Young, Kim Soo-Hyun, Choi Mi-Yeon, Park Joon Seong, Kim Hyeoung-Joon, Kim Sung-Hyun, Zang Dae Young, Oh Sukjoong, Kim Hawk, Do Young Rok, Kwak Jae-Yong, Kim Jeong-A, Kim Dae-Young, Mun Yeung-Chul, Lee Won Sik, Chang Myung Hee, Park Jinny, Kwon Ji Hyun, Kim Dong-Wook
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea.
Haematologica. 2016 Jun;101(6):717-23. doi: 10.3324/haematol.2015.139899. Epub 2016 Feb 17.
The aim of the Korean Imatinib Discontinuation Study was to identify predictors for safe and successful imatinib discontinuation. A total of 90 patients with a follow-up of ≥12 months were analyzed. After a median follow-up of 26.6 months after imatinib discontinuation, 37 patients lost the major molecular response. The probability of sustained major molecular response at 12 months and 24 months was 62.2% and 58.5%, respectively. All 37 patients who lost major molecular response were retreated with imatinib therapy for a median of 16.9 months, and all achieved major molecular response again at a median of 3.9 months after resuming imatinib therapy. We observed newly developed or worsened musculoskeletal pain and pruritus in 27 (30%) patients after imatinib discontinuation. Imatinib withdrawal syndrome was associated with a higher probability of sustained major molecular response (P=0.003) and showed a trend for a longer time to major molecular response loss (P=0.098). Positivity (defined as ≥ 17 positive chambers) of digital polymerase chain reaction at screening and longer imatinib duration before imatinib discontinuation were associated with a higher probability of sustained major molecular response. Our data demonstrated that the occurrence of imatinib withdrawal syndrome after imatinib discontinuation and longer duration of imatinib were associated with a lower rate of molecular relapse. In addition, minimal residual leukemia measured by digital polymerase chain reaction had a trend for a higher molecular relapse. (Trial registered at ClinicalTrials.gov: NCT01564836).
韩国伊马替尼停药研究的目的是确定伊马替尼安全、成功停药的预测因素。共分析了90例随访时间≥12个月的患者。伊马替尼停药后中位随访26.6个月,37例患者失去主要分子反应。12个月和24个月时持续主要分子反应的概率分别为62.2%和58.5%。所有37例失去主要分子反应的患者均接受伊马替尼治疗,中位治疗时间为16.9个月,恢复伊马替尼治疗后中位3.9个月均再次获得主要分子反应。我们观察到27例(30%)患者在伊马替尼停药后出现新的或加重的肌肉骨骼疼痛和瘙痒。伊马替尼撤药综合征与持续主要分子反应的较高概率相关(P=0.003),且显示出主要分子反应丧失时间较长的趋势(P=0.098)。筛查时数字聚合酶链反应阳性(定义为≥17个阳性管腔)以及伊马替尼停药前较长的伊马替尼使用时间与持续主要分子反应的较高概率相关。我们的数据表明,伊马替尼停药后伊马替尼撤药综合征的发生以及较长的伊马替尼使用时间与分子复发率较低相关。此外,通过数字聚合酶链反应测量的微小残留白血病有分子复发率较高的趋势。(该试验已在ClinicalTrials.gov注册:NCT01564836)