HRB Clinical Research Facility, National University of Ireland Galway & Trinity College Dublin,, University Road, Galway, Ireland.
Leukemia. 2012 May;26(5):959-62. doi: 10.1038/leu.2011.355. Epub 2011 Dec 13.
Nilotinib is a selective inhibitor of BCR-ABL approved for use in newly diagnosed and imatinib-resistant or -intolerant patients with chronic myeloid leukemia (CML) in chronic phase. In this study, 400 mg of nilotinib was administered twice daily to the patients with myeloid (MBP, n=105) or lymphoid blastic phase (LBP, n=31) CML. After a minimum follow-up of 24 months, major hematologic responses were observed in 60% (MBP) and 59% (LBP) of patients. Major cytogenetic responses (MCyR) were attained in 38% (MBP) and 52% (LBP) of patients; and complete cytogenetic responses in 30% and 32%, respectively. Median duration of MCyR was 10.8 (MBP) and 3.2 months (LBP). Median overall survival was 10.1 (MBP) and 7.9 (LBP) months with 12- and 24-month survival of 42% (MBP 44%, LBP 35%) and 27% (MBP 32%, LBP 10%), respectively. Twelve MBP patients and two LBP patients received subsequent stem cell transplantation. Myelosuppression was frequent, with grade 3/4 neutropenia, thrombocytopenia, and anemia in 68%, 63% and 47% of patients, respectively. Grade 3/4 hypophosphatemia, hyperbilirubinemia and lipase elevation were observed in 15%, 11% and 11% of patients, respectively. Nilotinib has significant efficacy in patients with BP CML, but given the limited long-term survival of these patients, novel agents are needed.
尼洛替尼是一种 BCR-ABL 的选择性抑制剂,已被批准用于治疗新诊断的、对伊马替尼耐药或不耐受的慢性髓性白血病(CML)慢性期患者。在这项研究中,400mg 尼洛替尼每天两次用于治疗骨髓(MBP,n=105)或淋巴母细胞(LBP,n=31)急变期 CML 患者。在至少 24 个月的随访后,60%(MBP)和 59%(LBP)的患者获得了主要血液学反应。38%(MBP)和 52%(LBP)的患者获得了主要细胞遗传学反应(MCyR);30%和 32%的患者分别获得完全细胞遗传学反应。MCyR 的中位持续时间分别为 10.8(MBP)和 3.2 个月(LBP)。中位总生存期分别为 10.1(MBP)和 7.9(LBP)个月,12 个月和 24 个月的生存率分别为 42%(MBP 44%,LBP 35%)和 27%(MBP 32%,LBP 10%)。12 名 MBP 患者和 2 名 LBP 患者随后接受了干细胞移植。骨髓抑制频繁,分别有 68%、63%和 47%的患者出现 3/4 级中性粒细胞减少、血小板减少和贫血;分别有 15%、11%和 11%的患者出现 3/4 级低磷血症、高胆红素血症和脂肪酶升高。尼洛替尼在急变期 CML 患者中具有显著疗效,但鉴于这些患者的长期生存有限,需要新的药物。