伊布替尼作为慢性淋巴细胞白血病患者的初始治疗方法。
Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia.
作者信息
Burger Jan A, Tedeschi Alessandra, Barr Paul M, Robak Tadeusz, Owen Carolyn, Ghia Paolo, Bairey Osnat, Hillmen Peter, Bartlett Nancy L, Li Jianyong, Simpson David, Grosicki Sebastian, Devereux Stephen, McCarthy Helen, Coutre Steven, Quach Hang, Gaidano Gianluca, Maslyak Zvenyslava, Stevens Don A, Janssens Ann, Offner Fritz, Mayer Jiří, O'Dwyer Michael, Hellmann Andrzej, Schuh Anna, Siddiqi Tanya, Polliack Aaron, Tam Constantine S, Suri Deepali, Cheng Mei, Clow Fong, Styles Lori, James Danelle F, Kipps Thomas J
机构信息
From the University of Texas MD Anderson Cancer Center, Houston (J.A.B.); Azienda Ospedaliera Niguarda Cà Granda (A.T.) and Università Vita-Salute San Raffaele and IRCCS Istituto Scientifico San Raffaele (P.G.), Milan, and the Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara (G.G.) - all in Italy; Wilmot Cancer Institute, University of Rochester, Rochester, NY (P.M.B.); Medical University of Lodz and Copernicus Memorial Hospital, Lodz (T.R.), the Department of Cancer Prevention, School of Public Health, Medical University of Silesia, Katowice (S.G.), and the Department of Hematology, University Clinical Center of Medical University of Gdansk, Gdansk (A.H.) - all in Poland; Tom Baker Cancer Centre, Calgary, AB, Canada (C.O.); Rabin Medical Center, Beilinson Hospital and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (O.B.), and Hadassah University Hospital, Hebrew University Medical School, Jerusalem (A.P.) - both in Israel; Leeds Teaching Hospitals, St. James Institute of Oncology, Leeds (P.H.), Kings College Hospital, London (S.D.), Royal Bournemouth Hospital, Bournemouth (H.M.), and University of Oxford, Oxford (A.S.) - all in the United Kingdom; Washington University School of Medicine, St. Louis (N.L.B.); Jiangsu Province Hospital, Nanjing, China (J.L.); North Shore Hospital, Auckland, New Zealand (D. Simpson); Stanford University School of Medicine, Stanford (S.C.), City of Hope National Medical Center, Duarte (T.S.), Pharmacyclics, Sunnyvale (D. Suri, M.C., F.C., L.S., D.F.J.), and Moores Cancer Center, University of California, San Diego, San Diego (T.J.K.) - all in California; St. Vincent's Hospital, University of Melbourne (H.Q.), and Peter MacCallum Cancer Centre and St. Vincent's Hospital (C.S.T.), Melbourne, VIC, Australia; Institute of Blood Pathology and Transfusion Medicine, National Academy of Medical Sciences of Ukraine, Lviv, Ukraine (Z.M.); Norton Cancer Institute, Louisville, KY (D.A.S.);
出版信息
N Engl J Med. 2015 Dec 17;373(25):2425-37. doi: 10.1056/NEJMoa1509388. Epub 2015 Dec 6.
BACKGROUND
Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma.
METHODS
We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee.
RESULTS
The median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib.
CONCLUSIONS
Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.).
背景
慢性淋巴细胞白血病（CLL）主要影响老年人，这些患者除了患有与疾病相关的免疫抑制和骨髓抑制外，通常还伴有其他并存疾病。我们开展了一项国际、开放标签、随机3期试验，以比较两种口服药物——伊布替尼和苯丁酸氮芥，用于先前未接受治疗的老年CLL或小淋巴细胞淋巴瘤患者。
方法
我们将269例年龄在65岁及以上、患有CLL或小淋巴细胞淋巴瘤且先前未接受治疗的患者随机分配，使其接受伊布替尼或苯丁酸氮芥治疗。主要终点为由独立审查委员会评估的无进展生存期。
结果
患者的中位年龄为73岁。在中位随访期18.4个月期间，伊布替尼组的无进展生存期显著长于苯丁酸氮芥组（中位无进展生存期：未达到 vs. 18.9个月），伊布替尼组疾病进展或死亡风险比苯丁酸氮芥组低84%（风险比，0.16；P<0.001）。伊布替尼显著延长了总生存期；伊布替尼组24个月时的估计生存率为98%，而苯丁酸氮芥组为85%，伊布替尼组的相对死亡风险比苯丁酸氮芥组低84%（风险比，0.16；P=0.001）。伊布替尼组的总缓解率高于苯丁酸氮芥组（86% vs. 35%，P<0.001）。伊布替尼组血红蛋白和血小板水平从基线值持续升高的比例更高。接受伊布替尼治疗的患者中至少20%发生的任何级别的不良事件包括腹泻、疲劳、咳嗽和恶心；接受苯丁酸氮芥治疗的患者中至少20%发生的不良事件包括恶心、疲劳、中性粒细胞减少、贫血和呕吐。在伊布替尼组，4例患者发生3级出血，1例患者发生4级出血。伊布替尼组共有87%的患者继续服用伊布替尼。
结论
在先前未接受治疗的CLL或小淋巴细胞淋巴瘤患者中，根据无进展生存期、总生存期、缓解率和血液学变量改善情况评估，伊布替尼优于苯丁酸氮芥。（由Pharmacyclics等资助；RESONATE - 2临床试验注册号，NCT01722487。）
Zotero 插件