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伊布替尼联合利妥昔单抗或化学免疫疗法治疗慢性淋巴细胞白血病
Ibrutinib–Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia


Tait D. Shanafelt ... 肿瘤 • 2019.08.01
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初治CLL伊布替尼联合利妥昔单抗优于常规免疫化疗

 

赵维莅

上海血液学研究所;上海交通大学医学院附属瑞金医院

 

慢性淋巴细胞白血病(CLL)是最常见的淋巴细胞恶性疾病之一。以氟达拉滨、环磷酰胺和利妥昔单抗(FCR)为代表的免疫化疗方案已成为70岁及以下初治CLL患者的标准治疗方案。FCR方案尤其对于免疫球蛋白重链可变区(IGHV)突变的CLL患者有效,使50%的IGHV突变患者的无进展生存时间超过8~10年。

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摘要


背景

有关未经治的慢性淋巴细胞白血病(CLL)患者接受伊布替尼联合利妥昔单抗治疗或标准化学免疫疗法(氟达拉滨、环磷酰胺和利妥昔单抗)的疗效比较,目前数据有限。

 

方法

在一项3期试验中,我们(以2∶1的比例)将≤70岁的未经治CLL患者随机分组,一组(在1个周期的单独伊布替尼治疗之后)接受6个周期的伊布替尼和利妥昔单抗治疗,之后接受伊布替尼治疗直至疾病进展,另一组接受6个周期的氟达拉滨、环磷酰胺和利妥昔单抗化学免疫治疗。主要终点是无进展生存期,次要终点是总生存期。我们在本文中报告了计划的期中分析的结果。

 

结果

共有529例患者被随机分组(伊布替尼联合利妥昔单抗组354例和化学免疫疗法组175例)。中位随访33.6个月时,伊布替尼联合利妥昔单抗治疗的无进展生存率分析结果优于化学免疫疗法(3年时,89.4% vs. 72.9%;进展或死亡的风险比,0.35;95%置信区间[CI],0.22~0.56;P<0.001),并且结果达到了试验方案规定的期中分析的疗效阈值。伊布替尼联合利妥昔单抗治疗的总生存率分析结果也优于化学免疫疗法(3年时,98.8% vs. 91.5%;死亡的风险比,0.17;95% CI,0.05~0.54;P<0.001)。在对无免疫球蛋白重链可变区(IGHV)突变的患者进行的亚组分析中,伊布替尼联合利妥昔单抗治疗的无进展生存率优于化学免疫疗法(3年时,90.7% vs. 62.5%;进展或死亡的风险比,0.26;95% CI,0.14~0.50)。在有IGHV突变的患者中,伊布替尼联合利妥昔单抗组和化学免疫疗法组的3年无进展生存率分别为87.7%和88.0%(进展或死亡的风险比,0.44;95% CI,0.14~1.36)。在两组中,3级或更高级别不良事件(不考虑因果关系)的发生率相似(伊布替尼联合利妥昔单抗组352例患者中的282例[80.1%]和化学免疫疗法组158例患者中的126例[79.7%]),而伊布替尼联合利妥昔单抗组的3级或更高级别感染性并发症的发生率低于化学免疫疗法组(37例[10.5%] vs. 32例[20.3%],P<0.001)。

 

结论

在≤70岁的未经治CLL患者中,伊布替尼联合利妥昔单抗组的无进展生存率和总生存率均优于标准化学免疫疗法组(由美国国立癌症研究所[National Cancer Institute]和Pharmacyclics资助;E1912在ClinicalTrials.gov注册号为NCT02048813)。





作者信息

Tait D. Shanafelt, M.D., Xin V. Wang, Ph.D., Neil E. Kay, M.D., Curtis A. Hanson, M.D., Susan O’Brien, M.D., Jacqueline Barrientos, M.D., Diane F. Jelinek, Ph.D., Esteban Braggio, Ph.D., Jose F. Leis, M.D., Ph.D., Cong C. Zhang, M.D., Steven E. Coutre, M.D., Paul M. Barr, M.D., Amanda F. Cashen, M.D., Anthony R. Mato, M.S.C.E., Avina K. Singh, M.D., Michael P. Mullane, M.D., Richard F. Little, M.D., Harry Erba, M.D., Ph.D., Richard M. Stone, M.D., Mark Litzow, M.D., and Martin Tallman, M.D.
From Stanford University, Stanford (T.D.S., S.E.C.), the University of California, Irvine, Medical Center, Orange (S.O.), and Kaiser Permanente National Cancer Institute Community Oncology Research Program (NCORP)–Permanente Medical Group, Oakland (C.C.Z.) — all in California; Dana–Farber Cancer Institute, Boston (X.V.W., R.M.S.); Mayo Clinic, Rochester (N.E.K., C.A.H., J.F.L., M.L.), and Minnesota Oncology, Burnsville (A.K.S.) — both in Minnesota; Northwell Health Cancer Institute, Donald and Barbara Zucker School of Medicine at Hofstra–Northwell, Lake Success (J.B.), and University of Rochester, Rochester (P.M.B.) — both in New York; Mayo Clinic, Phoenix, AZ (D.F.J., E.B.); Washington University School of Medicine, St. Louis (A.F.C.); Memorial Sloan Kettering Cancer Center, New York (A.R.M., M.T.); Aurora Cancer Care, West Allis, WI (M.P.M.); National Cancer Institute, Bethesda, MD (R.F.L.); and the University of Alabama, Tuscaloosa (H.E.). Address reprint requests to Dr. Shanafelt at the Division of Hematology, Department of Medicine, Stanford University School of Medicine, 300 Pasteur Dr., Rm. 3215, Stanford, CA 94025, or at tshana@stanford.edu.

 

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