From the University of Texas M.D. Anderson Cancer Center, Houston (M.L.W.); Maria Sklodowska-Curie National Research Institute of Oncology, Kraków (W.J.), and Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw (J.W.) - both in Poland; Skane University Hospital and Lund University, Lund, Sweden (M.J.); Concord Repatriation General Hospital, University of Sydney, Sydney (J.T.), and Royal Adelaide Hospital, Adelaide, SA (P.G.) - both in Australia; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli," Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna (P.L.Z.), and SC Ematologia, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin (C.B.) - both in Italy; the Fourth Department of Internal Medicine-Hematology, Charles University Hospital and Faculty of Medicine, Hradec Králové, Czech Republic (D.B.); Sarah Cannon Research Institute and Tennessee Oncology, Nashville (I.W.F.); John Theurer Cancer Center, Hackensack (A.G.), and Janssen Research and Development, Raritan (R.Q., T.H., S.D., A.H.) - both in New Jersey; Memorial Sloan Kettering Cancer Center, New York (P.A.H.); the Department of Hematology, Hôpital Necker, Assistance Publique-Hôpitaux de Paris and Institut Imagine, Université de Paris, INSERM Unité Mixte de Recherche 1183 (O.H.), and Institut Curie Comprehensive Cancer Center (S.L.G.), Paris, and Hospitalier Universitaire de Nantes, Centre de Recherche en Cancérologie et Immunologie Nantes Angers, INSERM, Université de Nantes, Nantes (S.L.G.) - all in France; the Department of Hematology, Hospital Universitario Infanta Leonor, Universidad Complutense, Madrid (J.-Á.H.-R.); Fudan University Shanghai Cancer Center, Shanghai (X.H.), and Key Laboratory of Carcinogenesis and Translational Research, Department of Lymphoma, Peking University Cancer Hospital and Institute, Beijing (Y.S., J.Z.) - both in China; the Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (S.J.K.); University Hospitals Plymouth NHS Trust, Plymouth (D.L.), and Kent and Canterbury Hospital, Canterbury (C.P.) - both in the United Kingdom; the Department of Hematology-Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo (Y.M.); Ankara University School of Medicine, Ankara, Turkey (M.Ö.); Hospital Israelita Albert Einstein, São Paulo (G.F.P.); the Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland (S.E.S.); the Research Institute of the McGill University Health Centre, McGill University, Montreal (J.M.S.); and Klinikum der Universität München, Ludwig Maximilian University of Munich, Munich, Germany (M.D.).
N Engl J Med. 2022 Jun 30;386(26):2482-2494. doi: 10.1056/NEJMoa2201817. Epub 2022 Jun 3.
Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma.
We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end point was progression-free survival as assessed by the investigators. Overall survival and safety were also assessed.
Among 523 patients, 261 were randomly assigned to receive ibrutinib and 262 to receive placebo. At a median follow-up of 84.7 months, the median progression-free survival was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P = 0.06). Overall survival was similar in the two groups. The incidence of grade 3 or 4 adverse events during treatment was 81.5% in the ibrutinib group and 77.3% in the placebo group.
Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged progression-free survival. The safety profile of the combined therapy was consistent with the known profiles of the individual drugs. (Funded by Janssen Research and Development and Pharmacyclics; SHINE ClinicalTrials.gov number, NCT01776840.).
伊布替尼是一种布鲁顿酪氨酸激酶抑制剂，与苯达莫司汀和利妥昔单抗联合应用，并在未经治疗的套细胞淋巴瘤老年患者中进行利妥昔单抗维持治疗后，可能具有临床获益。
我们将 65 岁或以上的患者随机分配接受伊布替尼（560mg，每天口服一次，直至疾病进展或出现不可接受的毒性作用）或安慰剂，联合六周期苯达莫司汀（90mg/平方米体表面积）和利妥昔单抗（375mg/平方米）。有客观反应（完全或部分缓解）的患者接受利妥昔单抗维持治疗，每 8 周给药，最多 12 个额外剂量。主要终点是研究者评估的无进展生存期。还评估了总生存期和安全性。
在 523 名患者中，261 名随机分配接受伊布替尼，262 名接受安慰剂。中位随访 84.7 个月时，伊布替尼组的中位无进展生存期为 80.6 个月，安慰剂组为 52.9 个月（疾病进展或死亡的风险比，0.75；95%置信区间，0.59 至 0.96；P=0.01）。伊布替尼组完全缓解率为 65.5%，安慰剂组为 57.6%（P=0.06）。两组总生存期相似。伊布替尼组治疗期间发生 3 级或 4 级不良事件的发生率为 81.5%，安慰剂组为 77.3%。
伊布替尼联合标准化疗免疫治疗显著延长了无进展生存期。联合治疗的安全性与各药物的已知特征一致。（由 Janssen Research and Development 和 Pharmacyclics 资助；SHINE ClinicalTrials.gov 编号，NCT01776840。）。
