Brentuximab vedotin plus cyclophosphamide, doxorubicin, etoposide, and prednisone followed by brentuximab vedotin consolidation in CD30-positive peripheral T-cell lymphomas: a multicentre, single-arm, phase 2 study.

IF 15.4 1区 医学 Q1 HEMATOLOGY Lancet Haematology Pub Date : 2024-09-01 Epub Date: 2024-07-24 DOI:10.1016/S2352-3026(24)00171-6
Alex F Herrera, Jasmine Zain, Kerry J Savage, Tatyana Feldman, Jonathan E Brammer, Lu Chen, Sandrine Puverel, Leslie Popplewell, Lihua Elizabeth Budde, Matthew Mei, Chitra Hosing, Ranjit Nair, Lori Leslie, Shari Daniels, Lacolle Peters, Stephen Forman, Steven Rosen, Larry Kwak, Swaminathan P Iyer
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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<sup>2</sup> intravenously on day 1, doxorubicin 50 mg/m<sup>2</sup> intravenously on day 1, etoposide 100 mg/m<sup>2</sup> 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. 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引用次数: 0

Abstract

Background: 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.

Methods: 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/m2 intravenously on day 1, doxorubicin 50 mg/m2 intravenously on day 1, etoposide 100 mg/m2 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 ClinicalTrials.gov (NCT03113500), and this cohort completed the trial. The trial is ongoing with the enrolment of a new cohort.

Findings: 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 mm3 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.

Interpretation: 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.

Funding: SeaGen, Leukemia and Lymphoma Society, Lymphoma Research Foundation, and the National Cancer Institute of the National Institutes of Health.

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在 CD30 阳性外周 T 细胞淋巴瘤中使用布伦妥昔单抗维多汀加环磷酰胺、多柔比星、依托泊苷和泼尼松,然后使用布伦妥昔单抗维多汀巩固治疗:一项多中心、单臂、2 期研究。
背景:CD30在无性大细胞淋巴瘤中普遍表达,在其他一些外周T细胞淋巴瘤亚型中也有表达。在CD30阳性外周T细胞淋巴瘤患者的初始治疗中加入布伦妥昔单抗维多汀可延长无进展生存期,但仍有改进的余地,尤其是非无性大细胞淋巴瘤亚型患者:我们在美国和加拿大的五个学术中心开展了一项多中心、国际性、单臂、2期试验,以评估CHEP-BV(环磷酰胺、多柔比星、泼尼松、布伦妥昔单抗维多汀和依托泊苷)治疗CD30表达外周T细胞淋巴瘤患者,然后进行布伦妥昔单抗维多汀巩固治疗的安全性和活性。年龄在18岁或18岁以上、新确诊、未经治疗的CD30阳性外周T细胞淋巴瘤患者,东部合作肿瘤学组评分为0-2分,器官功能正常,均有资格接受6个计划周期的CHEP-BV治疗(即1-8毫克/千克布伦妥昔单抗)、1-8 mg/kg brentuximab vedotin,第1天静脉注射;环磷酰胺750 mg/m2,第1天静脉注射;多柔比星50 mg/m2,第1天静脉注射;依托泊苷100 mg/m2,第1-3天每天静脉注射;泼尼松100 mg,第1-5天每天口服),并预防性使用G-CSF。对治疗有反应的患者可在自体造血干细胞移植(HSCT)后或直接在CHEP-BV后接受布伦妥西单抗维多汀巩固治疗,最多可再延长10个周期。主要终点是接受研究治疗并完成安全评估期(以确认CHEP-BV中布仑妥昔单抗维多汀的2期推荐剂量)的参与者在3+3安全引导期间的不可接受毒性,以及接受研究治疗并进行反应评估的参与者在CHEP-BV诱导治疗后的完全反应率。该研究已在ClinicalTrials.gov(NCT03113500)上注册,该队列已完成试验。该试验正在进行中,并将招募新的组群:54名患者通过了资格筛选,48名符合研究条件。参与者(18 名[38%]女性和 30 名[63%]男性;34 名[71%]白人、4 名[8%]黑人、5 名[10%]亚裔、10 名[21%]西班牙裔和 37 名[77%]非西班牙裔)于 2017 年 12 月 4 日至 2021 年 6 月 14 日期间被招募和入组,并随访至 2023 年 8 月 25 日锁定数据库进行分析。48名参与者可进行毒性评估,47名参与者可进行应答评估(一名参与者在应答评估前死于COVID-19)。在安全先导期,6 名参与者中有 1 人出现了不可接受的毒性(即一名参与者的血小板计数为 3,骨髓广泛受累),CHEP-BV 中提议的 2 期剂量为 1-8 mg/kg 布伦妥昔单抗维多汀得到确认。CHEP-BV结束时,47名参与者中有37人完全应答,完全应答率为79%(95% CI 64-89)。与CHEP-BV相关的最常见的3级或3级以上毒性反应是中性粒细胞减少(48例中有14例[29%])、白细胞减少(11例[23%])、贫血(10例[21%])、发热性中性粒细胞减少(10例[21%])、淋巴细胞减少(9例[19%])和血小板减少(9例[19%])。无治疗相关死亡病例:解读:对于主要表达CD30的外周T细胞淋巴瘤(非非典型大细胞淋巴瘤除外)患者,CHEP-BV(伴或不伴自体造血干细胞移植)后布伦妥昔单抗维多汀巩固治疗是安全和有效的:经费来源:SeaGen、白血病与淋巴瘤协会、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。
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来源期刊
Lancet Haematology
Lancet Haematology HEMATOLOGY-
CiteScore
26.00
自引率
0.80%
发文量
323
期刊介绍: Launched in autumn 2014, The Lancet Haematology is part of the Lancet specialty journals, exclusively available online. This monthly journal is committed to publishing original research that not only sheds light on haematological clinical practice but also advocates for change within the field. Aligned with the Lancet journals' tradition of high-impact research, The Lancet Haematology aspires to achieve a similar standing and reputation within its discipline. It upholds the rigorous reporting standards characteristic of all Lancet titles, ensuring a consistent commitment to quality in its contributions to the field of haematology.
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