尼洛替尼与伊马替尼一线治疗初发慢性髓性白血病患者的比较研究  

Comparison of nilotinib vs imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase

作　　者：于露[1] 秦亚溱[1] 赖悦云[1] 石红霞[1] 黄晓军[1] 侯悦[1] 江倩[1] Yu Lu;Qin Yazhen;Lai Yueyun;Shi Hongxia;Huang Xiaojun;Hou Yue;Jiang Qian(Peking University People’s Hospital,Peking University Institute of Hematology,National Clinical Research Center for Hematologic Disease,Beijing 100044,China)

机构地区：[1]北京大学人民医院、北京大学血液病研究所、国家血液系统疾病临床医学研究中心,100044

出　　处：《中华血液学杂志》2019年第12期996-1002,共7页Chinese Journal of Hematology

基　　金：国家自然科学基金(81770161)。

摘　　要：目的比较尼洛替尼与伊马替尼一线治疗初发慢性髓性白血病(CML)慢性期(CP)患者的细胞遗传学和分子学反应获得率、预后及血液学不良反应的差异。方法回顾性分析2006年1月至2018年12月诊治的初诊且尼洛替尼或伊马替尼作为一线治疗的CML-CP患者的连续病例资料。结果共524例患者纳入研究,其中伊马替尼治疗组439例(83.8%),尼洛替尼治疗组85例(16.2%)。与伊马替尼组相比,尼洛替尼组患者更为年轻(P=0.019),Sokal积分中/高危患者(P<0.001)、WBC≥100×109/L(P<0.001)、HGB<120 g/L(P<0.001)、骨髓原始细胞(P=0.026)、脾脏可触及肿大(P<0.001)比例显著增高,诊断距服用TKI时间显著延长(P=0.003)。中位治疗57(3~153)个月,与伊马替尼组相比,尼洛替尼组患者更快、更高比例获得完全细胞遗传学反应(CCyR)(P=0.011)、主要分子学反应(MMR)(P=0.001)和分子学反应4.5(MR4.5)(P=0.046)。两组间6年无治疗失败生存(FFS)、无疾病进展生存(PFS)和总生存(OS)率差异均无统计学意义(P>0.05)。多因素分析显示,服用伊马替尼是获得CCyR(OR=0.6,95%CI 0.5~0.8,P=0.001)、MMR(OR=0.6,95%CI 0.5~0.8,P=0.001)和MR4.5(OR=0.6,95%CI 0.5~0.9,P=0.032)的不利因素,并与较差的FFS(OR=1.9,95%CI 1.0~3.4,P=0.041)显著相关。Sokal中/高危与较低的细胞遗传学和分子学反应获得率和较差的FFS、PFS、OS相关。此外,男性、诊断时WBC≥100×10^9/L或HGB<120 g/L也与较低的细胞遗传学和分子学反应获得率和(或)较差的FFS显著相关。严重的白细胞减少和血小板减少与药物种类无关。结论对于初诊CML-CP患者,与伊马替尼相比,尼洛替尼一线治疗能够更快、更早地获得细胞遗传学反应和深层分子学反应,并显著改善FFS。Objective To compare the cytogenetic and molecular responses,outcomes and severe hematologic toxicity of nilotinib and imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase(CML-CP).Methods Newly diagnosed CML-CP patients were consecutively recruited from January 2006 to December 2018 who received nilotinib and imatinib as first-line treatment.Clinical data were retrospectively analyzed.Results A total of 524 patients were classified into 439(83.8%)receiving imatinib and 85(16.2%)receiving nilotinib.Comparing with imatinib group,patients in nilotinib group were much younger(P=0.019)and more with intermediate and high Sokal risks(P<0.001),WBC≥100×109/L(P<0.001),HGB<120 g/L(P<0.001),blast cells in bone marrow(P=0.026),splenomegaly(P<0.001)by physical examination at diagnosis,and longer interval from diagnosis to TKI treatment(P=0.003).With a median TKI duration of 57(range 3-153)months,the probabilities of complete cytogenetic response(CCyR)(P=0.011),major molecular response(MMR)(P=0.001)and MR4.5(P=0.046)were much higher in nilotinib group than those in imatnib according to each risk group.There is no statistical significance on probabilities of failure free survival(FFS),progression free survival(PFS)and overall survival(OS)at 6 years between the two groups.Multivariate analyses showed that imatinib was an adverse factor associated with achieving CCyR(OR=0.6,95%CI 0.5-0.8,P=0.001),MMR(OR=0.6,95%CI 0.5-0.9,P=0.032)and MR4.5(OR=0.6,95%CI 0.5-0.9,P=0.032)and poor FFS(OR=1.9,95%CI 1.0-3.4,P=0.041).In addition,Sokal score was an independent factor affecting cytogenetic and molecular responses,treatment failure,disease progression and survival.Male,WBC≥100×10^9/L or HGB<120 g/L at diagnosis were significantly associated with lower cytogenetic and molecular response rates and/or poor FFS.The severe hematologic adverse events were not associated with different TKIs.Conclusions Nilotinib reaches to the faster and deeper cytogenetic and molecular responses and signifi

关 键 词：白血病 髓系 慢性 BCR-ABL阳性 尼洛替尼 伊马替尼 

分 类 号：R733[医药卫生—肿瘤]