贝林妥欧单抗联合化疗治疗儿科高危霍奇金淋巴瘤。

Brentuximab Vedotin with Chemotherapy in Pediatric High-Risk Hodgkin's Lymphoma.

机构信息

From the Department of Pediatrics, Emory University School of Medicine (S.M.C., F.G.K.), and Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta (S.M.C., F.G.K.) - both in Atlanta; the Department of Biostatistics, Children's Oncology Group, Statistics and Data Center, University of Florida, Gainesville (Q.P., Y.W.), and the Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville (B.S.H.); the Institute for Clinical Research and Health Policy Studies and Tufts Cancer Center, Tufts Medical Center, Boston (S.K.P.); the Department of Radiation Oncology, Princess Margaret Cancer Centre and University of Toronto (D.H.), and the Division of Hematology-Oncology, Hospital for Sick Children and University of Toronto (A.P.), Toronto, and the Department of Radiation Oncology, Centre Hospitalier de l'Université de Montréal, Montreal (A.-M.C.) - all in Canada; Imaging and Radiation Oncology Core Rhode Island, Lincoln (K.M.); the Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston (T.H.); the Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison (S.C.); the Department of Pediatrics, Children's National Hospital, and George Washington School of Medicine and Health Sciences, Washington, DC (H.D.); the Department of Pediatrics, University of Chicago Pritzker School of Medicine, Comer Children's Hospital, Chicago (T.O.H.); and the Department of Pediatrics, Roswell Park Comprehensive Cancer Center, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY (K.M.K.).

出版信息

N Engl J Med. 2022 Nov 3;387(18):1649-1660. doi: 10.1056/NEJMoa2206660.

DOI:10.1056/NEJMoa2206660

PMID:36322844

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9945772/

Abstract

BACKGROUND

In adults with advanced-stage Hodgkin's lymphoma, the CD30-directed antibody-drug conjugate brentuximab vedotin combined with multiagent chemotherapy has been shown to have greater efficacy, but also more toxic effects, than chemotherapy alone. The efficacy of this targeted therapy approach in children and adolescents with Hodgkin's lymphoma is unclear.

METHODS

We conducted an open-label, multicenter, randomized, phase 3 trial involving patients 2 to 21 years of age with previously untreated Hodgkin's lymphoma of stage IIB with bulk tumor or stage IIIB, IVA, or IVB. Patients were assigned to receive five 21-day cycles of brentuximab vedotin with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (brentuximab vedotin group) or the standard pediatric regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (standard-care group). Slow-responding lesions, defined by a score of 4 or 5 (on a 5-point scale, with scores of 1 to 3 indicating rapid-responding lesions), were identified on centrally reviewed positron-emission tomography-computed tomography after two cycles. Involved-site radiation therapy was administered after the fifth cycle of therapy to slow-responding lesions and to large mediastinal adenopathy that was present at diagnosis. The primary end point was event-free survival, defined as the time until disease progression occurred, relapse occurred, a second malignant neoplasm developed, or the patient died. Safety and overall survival were assessed.

RESULTS

Of 600 patients who were enrolled across 153 institutions, 587 were eligible. At a median follow-up of 42.1 months (range, 0.1 to 80.9), the 3-year event-free survival was 92.1% (95% confidence interval [CI], 88.4 to 94.7) in the brentuximab vedotin group, as compared with 82.5% (95% CI, 77.4 to 86.5) in the standard-care group (hazard ratio for event or death, 0.41; 95% CI, 0.25 to 0.67; P<0.001). The percentage of patients who received involved-site radiation therapy did not differ substantially between the brentuximab vedotin group and the standard-care group (53.4% and 56.8%, respectively). Toxic effects were similar in the two groups. Overall survival at 3 years was 99.3% (95% CI, 97.3 to 99.8) in the brentuximab vedotin group and 98.5% (95% CI, 96.0 to 99.4) in the standard-care group.

CONCLUSIONS

The addition of brentuximab vedotin to standard chemotherapy resulted in superior efficacy, with a 59% lower risk of an event or death, and no increase in the incidence of toxic effects at 3 years. (Funded by the National Institutes of Health and others; AHOD1331 ClinicalTrials.gov number, NCT02166463.).

摘要

背景

在患有晚期霍奇金淋巴瘤的成年人中，与单独化疗相比，靶向 CD30 的抗体药物偶联物 Brentuximab vedotin 联合多药化疗显示出更大的疗效，但也有更多的毒副作用。这种靶向治疗方法在儿童和青少年霍奇金淋巴瘤患者中的疗效尚不清楚。

方法

我们开展了一项开放标签、多中心、随机、3 期临床试验，纳入了 2 至 21 岁、患有初治 IIB 期伴肿块肿瘤或 IIIB、IVA 或 IVB 期的霍奇金淋巴瘤的患者。患者被分配接受五个 21 天周期的 Brentuximab vedotin 联合多柔比星、长春新碱、依托泊苷、泼尼松和环磷酰胺（Brentuximab vedotin 组）或标准儿科方案的多柔比星、博来霉素、长春新碱、依托泊苷、泼尼松和环磷酰胺（标准治疗组）。在两个周期后，中心审查的正电子发射断层扫描-计算机断层扫描（PET-CT）上发现评分 4 或 5 的缓慢反应病灶（评分 1 至 3 表示快速反应病灶）。在第五个周期的治疗后，对缓慢反应病灶和大纵隔淋巴结肿大（在诊断时存在）进行受累部位放射治疗。主要终点是无事件生存，定义为疾病进展、复发、发生第二恶性肿瘤或患者死亡的时间。评估了安全性和总生存情况。

结果

在 153 家机构中，共有 600 名患者入组，其中 587 名符合条件。在中位随访 42.1 个月（范围 0.1 至 80.9）后，Brentuximab vedotin 组的 3 年无事件生存率为 92.1%（95%置信区间 [CI]，88.4 至 94.7），标准治疗组为 82.5%（95% CI，77.4 至 86.5）（事件或死亡风险比，0.41；95%CI，0.25 至 0.67；P<0.001）。Brentuximab vedotin 组和标准治疗组接受受累部位放射治疗的患者比例差异不大（分别为 53.4%和 56.8%）。两组的毒性作用相似。Brentuximab vedotin 组 3 年总生存率为 99.3%（95%CI，97.3 至 99.8），标准治疗组为 98.5%（95%CI，96.0 至 99.4）。