Iriyama Noriyoshi, Ohashi Kazuteru, Hashino Satoshi, Kimura Shinya, Nakaseko Chiaki, Takano Hina, Hino Masayuki, Uchiyama Michihiro, Morita Satoshi, Sakamoto Junichi, Sakamaki Hisashi, Inokuchi Koiti
Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Japan.
Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan.
Intern Med. 2018 Jan 1;57(1):17-23. doi: 10.2169/internalmedicine.9035-17. Epub 2017 Oct 16.
Objective The aim of this study was to prospectively investigate the efficacy and safety profiles of low-dose dasatinib therapy (50 mg once daily). Methods Patients with chronic myeloid leukemia in the chronic phase (CML-CP) who were being treated with low-dose imatinib (≤200 mg/day), but were resistant to this agent were enrolled in the current study (referred to as the LD-CML study). Results There subjects included 9 patients (4 men and 5 women); all were treated with dasatinib at a dose of 50 mg once daily. Among 8 patients who had not experienced major molecular response (MMR; BCR-ABL1 transcript ≤0.1% according to International Scale [IS]) at study enrollment, 5 attained MMR by 12 months. In particular, 3 of 9 patients demonstrated a deep molecular response (DMR; IS ≤0.0069%) by 18 months. Five patients developed lymphocytosis accompanied by cytotoxic lymphocyte predominance. There was no mortality or disease progression, and all continue to receive dasatinib therapy at 18 months with only 2 patients requiring dose reduction. Toxicities were mild-to-moderate, and pleural effusion was observed in 1 patient (grade 1). Conclusion Low-dose dasatinib can attain MMR and DMR without severe toxicity in patients with CML-CP who are unable to achieve MMR with low-dose imatinib. Switching to low-dose dasatinib should therefore be considered for patients in this setting, especially if they are otherwise considering a cessation of treatment.
目的 本研究旨在前瞻性地调查低剂量达沙替尼疗法(每日一次,50毫克)的疗效和安全性。方法 将正在接受低剂量伊马替尼(≤200毫克/天)治疗但对该药物耐药的慢性期慢性髓性白血病(CML-CP)患者纳入本研究(称为LD-CML研究)。结果 受试者包括9名患者(4名男性和5名女性);均接受每日一次50毫克剂量的达沙替尼治疗。在研究入组时未达到主要分子反应(MMR;根据国际标准[IS],BCR-ABL1转录本≤0.1%)的8名患者中,5名在12个月时达到MMR。特别是,9名患者中有3名在18个月时表现出深度分子反应(DMR;IS≤0.0069%)。5名患者出现淋巴细胞增多,伴有细胞毒性淋巴细胞占优势。没有死亡或疾病进展,所有患者在18个月时继续接受达沙替尼治疗,只有2名患者需要减量。毒性为轻至中度,1名患者出现胸腔积液(1级)。结论 对于无法通过低剂量伊马替尼达到MMR的CML-CP患者,低剂量达沙替尼可在无严重毒性的情况下达到MMR和DMR。因此,对于这种情况下的患者,尤其是那些否则正在考虑停止治疗的患者,应考虑改用低剂量达沙替尼。