From the Division of Hematology, Mayo Clinic, Rochester, MN (S.M.A.); the University of Manchester and the Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom (J.R.); BC Cancer Centre for Lymphoid Cancer, Vancouver (J.M.C., K.J.S.); Maria Sklodowska-Curie National Research Institute of Oncology, Krakow (M.D.-D.), and the Department of Experimental Hematology, Medical University of Lodz, Lodz (P.S.) - both in Poland; the Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (W.-S.K.), and the Department of Hematology-Oncology, Center for Hematologic Malignancy, National Cancer Center, Goyang (H.-S.E.) - both in South Korea; Research and Innovation Department, Antoine-Lacassagne Cancer Center, Nice, France (A.G.); the University of Tennessee Graduate School of Medicine, Knoxville (R.R.); Wilmot Cancer Institute, University of Rochester, Rochester (J.W.F.), and the Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York (D.J.S.) - both in New York; the Department of Medicine, Division of Oncology, Stanford University, Stanford, CA (R.A.); the Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen (M.H.); the Division of Blood Disorders, Rutgers Cancer Institute of New Jersey, New Brunswick (A.M.E.); Washington University School of Medicine Siteman Cancer Center, St. Louis (N.L.B.); Massachusetts General Hospital, Boston (J.S.A.), and Takeda Development Center Americas, Lexington (C.D., F.C.) - both in Massachusetts; and Seagen, Bothell, WA (K.F., M.P.).
N Engl J Med. 2022 Jul 28;387(4):310-320. doi: 10.1056/NEJMoa2206125. Epub 2022 Jul 13.
Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.
We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed.
A total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = 0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up.
Patients who received A+AVD for the treatment of stage III or IV Hodgkin's lymphoma had a survival advantage over those who received ABVD. (Funded by Takeda Development Center Americas and Seagen; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.).
在一项涉及未经治疗的 III 期或 IV 期经典霍奇金淋巴瘤患者的试验中，与多柔比星、博来霉素、长春碱和达卡巴嗪（ABVD）相比，一线治疗采用靶向 CD30 的抗体药物偶联物 Brentuximab Vedotin（BV）加多柔比星、长春碱和达卡巴嗪（A+AVD）可带来长期无进展生存获益。一项计划中的中期分析表明总生存存在潜在获益；现在可提供中位随访 6 年的随访数据。
我们以 1:1 的比例随机分配患者接受最多 6 个周期的 A+AVD 或 ABVD 治疗。主要终点是改良的无进展生存，先前已报告过。关键次要终点是在意向治疗人群中的总生存。同时还评估了安全性。
共有 664 例患者被分配接受 A+AVD，670 例患者接受 ABVD。在中位随访 73.0 个月时，A+AVD 组有 39 例患者和 ABVD 组有 64 例患者死亡（风险比，0.59；95%置信区间 [CI]，0.40 至 0.88；P=0.009）。A+AVD 组的 6 年总生存率估计为 93.9%（95%CI，91.6 至 95.5），ABVD 组为 89.4%（95%CI，86.6 至 91.7）。与 ABVD 相比，A+AVD 组的无进展生存率更长（疾病进展或死亡的风险比，0.68；95%CI，0.53 至 0.86）。与 ABVD 组相比，A+AVD 组接受后续治疗（包括移植）的患者更少，且 A+AVD 组报告的第二癌症更少（分别为 23 例和 32 例）。在观察到 A+AVD 组发热性中性粒细胞减少症发生率增加后，建议进行粒细胞集落刺激因子的一级预防。与 ABVD 相比，A+AVD 组发生周围神经病变的患者更多，但在最后一次随访时，两组大多数患者的事件均已缓解或改善。
接受 A+AVD 治疗 III 期或 IV 期霍奇金淋巴瘤的患者比接受 ABVD 治疗的患者具有生存优势。（由武田开发中心美洲公司和 Seagen 公司资助；ECHELON-1 临床试验.gov 编号，NCT01712490；EudraCT 编号，2011-005450-60。）
