CD30 expression is universal in anaplastic large-cell lymphoma and is expressed in some other peripheral T-cell lymphoma subtypes. Incorporation of brentuximab vedotin into initial therapy for people with CD30-positive peripheral T-cell lymphomas prolonged progression-free survival, but there is room for improvement, especially for people with non-anaplastic large-cell lymphoma subtypes. We conducted a multicentre, international, single-arm, phase 2 trial to evaluate the safety and activity of CHEP–BV (cyclophosphamide, doxorubicin, prednisone, brentuximab vedotin, and etoposide) followed by brentuximab vedotin consolidation in patients with CD30-expressing peripheral T-cell lymphomas across five academic centres in the USA and Canada. Adults aged 18 years or older with newly diagnosed, untreated CD30-positive peripheral T-cell lymphomas, Eastern Cooperative Oncology Group score of 0–2, and adequate organ function were eligible to receive six planned cycles of CHEP–BV (ie, 1·8 mg/kg brentuximab vedotin intravenously on day 1, cyclophosphamide 750 mg/m intravenously on day 1, doxorubicin 50 mg/m intravenously on day 1, etoposide 100 mg/m daily intravenously on days 1–3, and prednisone 100 mg daily orally on days 1–5) with prophylactic G-CSF. Patients who responded to the treatment could receive brentuximab vedotin consolidation for up to ten additional cycles either after autologous haematopoietic stem-cell transplantation (HSCT) or directly after CHEP–BV. The primary endpoints were unacceptable toxicity during a 3-plus-3 safety lead-in in participants who received study treatment and completed the safety evaluation period (to confirm the recommended phase 2 dose of brentuximab vedotin in CHEP–BV) and the complete response rate after CHEP–BV induction therapy in participants who received study treatment and had response evaluation. The study was registered at (), and this cohort completed the trial. The trial is ongoing with the enrolment of a new cohort. 54 patients were screened for eligibility and 48 were eligible for the study. The participants (18 [38%] women and 30 [63%] men; 34 [71%] White, four [8%] Black, five [10%] Asian, ten [21%] Hispanic, and 37 [77%] non-Hispanic people) were recruited and enrolled between Dec 4, 2017, and June 14, 2021, and followed up until Aug 25, 2023, when the database was locked for analysis. 48 participants were evaluable for toxicity, and 47 were evaluable for response (one participant died from COVID-19 before response assessment). During the safety lead-in, one of six participants had an unacceptable toxicity (ie, platelet count <10 000 per mm in a participant with extensive bone marrow involvement), and the proposed phase 2 dose of 1·8 mg/kg brentuximab vedotin in CHEP–BV was confirmed. At completion of CHEP–BV, 37 of 47 participants had complete response, yielding a complete response rate of 79% (95% CI 64–89). The most common CHEP–BV-related toxicities of grade 3 or higher were neutropenia (14 [29%] of 48), leukopenia (11 [23%]), anaemia (ten [21%]), febrile neutropenia (ten [21%]), lymphopenia (nine [19%]), and thrombocytopenia (nine [19%]). There were no treatment-related deaths. In patients with mostly CD30-expressing peripheral T-cell lymphomas other than non-anaplastic large-cell lymphoma, CHEP–BV (with or without autologous HSCT) followed by brentuximab vedotin consolidation was safe and active. SeaGen, Leukemia and Lymphoma Society, Lymphoma Research Foundation, and the National Cancer Institute of the National Institutes of Health.

中文翻译：

---

Brentuximab vedotin 加环磷酰胺、阿霉素、依托泊苷和泼尼松治疗 CD30 阳性外周 T 细胞淋巴瘤，随后进行 brentuximab vedotin 巩固治疗：一项多中心、单臂、2 期研究


CD30 表达在间变性大细胞淋巴瘤中普遍存在，并在其他一些外周 T 细胞淋巴瘤亚型中表达。将brentuximab vedotin纳入CD30阳性外周T细胞淋巴瘤患者的初始治疗可延长无进展生存期，但仍有改进的空间，特别是对于非间变性大细胞淋巴瘤亚型患者。我们进行了一项多中心、国际、单臂、2 期试验，以评估 CHEP-BV（环磷酰胺、多柔比星、泼尼松、brentuximab vedotin 和依托泊苷）随后对表达 CD30 的外周 T 患者进行 brentuximab vedotin 巩固治疗的安全性和活性。 -美国和加拿大五个学术中心的细胞淋巴瘤。 18 岁或以上的新诊断、未经治疗的 CD30 阳性外周 T 细胞淋巴瘤、东部肿瘤合作组评分为 0-2 且器官功能良好的成年人有资格接受 6 个计划周期的 CHEP-BV（即 1·第 1 天静脉注射 8 mg/kg brentuximab vedotin，第 1 天静脉注射环磷酰胺 750 mg/m，第 1 天静脉注射阿霉素 50 mg/m，第 1-3 天每天静脉注射依托泊苷 100 mg/m，每天口服泼尼松 100 mg第 1-5 天）使用预防性 G-CSF。对治疗有反应的患者可以在自体造血干细胞移植 (HSCT) 后或直接在 CHEP-BV 后接受最多十个周期的 brentuximab vedotin 巩固治疗。 主要终点是接受研究治疗并完成安全性评估期（以确认 CHEP-BV 中 brentuximab vedotin 的推荐 2 期剂量）的参与者在 3+3 安全导入期间出现的不可接受的毒性和完全缓解率在接受研究治疗并进行反应评估的参与者中进行 CHEP-BV 诱导治疗后。该研究在 () 注册，该队列完成了试验。该试验正在进行中，并招募了新的队列。 54 名患者接受了资格筛查，其中 48 名患者符合研究资格。参与者（18 [38%] 女性和 30 [63%] 男性；34 [71%] 白人，4 [8%] 黑人，5 [10%] 亚洲人，10 [21%] 西班牙裔，37 [77%] ]非西班牙裔人）在2017年12月4日至2021年6月14日期间招募和入组，并随访至2023年8月25日，此时数据库被锁定进行分析。 48 名参与者可进行毒性评估，47 名参与者可进行反应评估（一名参与者在反应评估前死于 COVID-19）。在安全导入期间，六名参与者中的一名出现了不可接受的毒性（即，一名患有广泛骨髓受累的参与者的血小板计数为 <10 000/mm），建议的 2 期剂量为 1·8 mg/kg brentuximab vedotin在 CHEP-BV 中得到证实。完成 CHEP-BV 后，47 名参与者中有 37 名获得完全缓解，完全缓解率为 79% (95% CI 64-89)。最常见的 3 级或以上 CHEP-BV 相关毒性包括中性粒细胞减少症（48 例中有 14 例 [29%]）、白细胞减少症（11 例 [23%]）、贫血（10 例 [21%]）、发热性中性粒细胞减少症（10 例 [21]） %]）、淋巴细胞减少症（9 例 [19%]）和血小板减少症（9 例 [19%]）。没有出现与治疗相关的死亡。 对于大多数表达 CD30 的外周 T 细胞淋巴瘤而非非间变性大细胞淋巴瘤的患者，CHEP-BV（伴或不伴自体 HSCT）随后进行 brentuximab vedotin 巩固治疗是安全且有效的。 SeaGen、白血病和淋巴瘤协会、淋巴瘤研究基金会和美国国立卫生研究院国家癌症研究所。