Ishikawa Jun, Matsumura Itaru, Kawaguchi Tatsuya, Kuroda Junya, Nakamae Hirohisa, Miyamoto Toshihiro, Matsuoka Ken-Ichi, Shibayama Hirohiko, Hino Masayuki, Hirase Chikara, Kamimura Tomohiko, Shimose Takayuki, Akashi Koichi, Kanakura Yuzuru
Department of Hematology, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan.
Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University, Osaka, Japan.
Int J Hematol. 2018 May;107(5):535-540. doi: 10.1007/s12185-018-2401-y. Epub 2018 Jan 23.
We evaluated the efficacy and safety of switching to nilotinib in CML-CP patients who had achieved MMR with continuous detectable BCR-ABL1 transcript levels after long-term imatinib treatment. Patients who had achieved MMR, but not deep molecular response (DMR), after > 18 months from the initiation of imatinib received nilotinib 400 mg twice daily for up to 24 months. BCR-ABL1 transcript levels were assessed every 3 months. Thirty-eight patients with a median age of 57.5 years (range 22-76 years) were evaluated. Twenty-seven patients completed 24 months of nilotinib treatment; 11 discontinued nilotinib due to retraction of consent (three patients), loss of MMR (1), intolerance (3) or AEs (5). Twenty patients [52.6%, (90% CI 38.2-66.7%)] achieved DMR. The cumulative incidence of achieving DMR by the time of 3, 6, 9, 12, 15, 18, and 21 months was 22.9, 37.7, 47.0, 53.7, 53.7, 53.7, and 53.7%, respectively. Adverse events were consistent with those reported in other nilotinib studies. Patients experienced each of the following cardiovascular complications: atrial fibrillation (G2), chest tightness and dyspnea (G1), myocardial infarction (G2) and heart failure (G3) (n = 1 for each complication). This study indicates nilotinib achieves strong, rapid induction of DMR for patients who achieved MMR after long-term imatinib therapy.
我们评估了在长期接受伊马替尼治疗后达到主要分子反应(MMR)但BCR-ABL1转录水平持续可检测的慢性期慢性髓性白血病(CML-CP)患者中换用尼罗替尼的疗效和安全性。在伊马替尼治疗开始>18个月后达到MMR但未达到深度分子反应(DMR)的患者接受每日两次400 mg尼罗替尼治疗,最长24个月。每3个月评估一次BCR-ABL1转录水平。评估了38例患者,中位年龄为57.5岁(范围22 - 76岁)。27例患者完成了24个月的尼罗替尼治疗;11例因撤回同意(3例患者)、MMR丧失(1例)、不耐受(3例)或不良事件(5例)而停用尼罗替尼。20例患者[52.6%,(90%置信区间38.2 - 66.7%)]达到DMR。在3、6、9、12、15、18和21个月时达到DMR的累积发生率分别为22.9%、37.7%、47.0%、53.7%、53.7%、53.7%和53.7%。不良事件与其他尼罗替尼研究中报告的一致。患者经历了以下心血管并发症:心房颤动(2级)、胸闷和呼吸困难(1级)、心肌梗死(2级)和心力衰竭(3级)(每种并发症各1例)。本研究表明,尼罗替尼可为长期伊马替尼治疗后达到MMR的患者实现强烈、快速的DMR诱导。