背景:CD30表达在间变性大细胞淋巴瘤中是普遍的,在其他一些外周T细胞淋巴瘤亚型中也有表达。将苯妥昔单抗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,但是还有改进的空间,特别是对于患有非间变性大细胞淋巴瘤亚型的人。
方法:我们进行了多中心,国际,单臂,评估CHEP-BV(环磷酰胺,阿霉素,泼尼松,Brentuximabvedotin,和依托泊苷),然后在美国和加拿大的五个学术中心中,在表达CD30的外周T细胞淋巴瘤患者中进行本妥昔单抗维多汀巩固。18岁或以上新诊断的成年人,未经治疗的CD30阳性外周T细胞淋巴瘤,东部肿瘤协作组得分为0-2,并且有足够的器官功能有资格接受六个计划周期的CHEP-BV(即,第1天静脉注射1·8mg/kg本妥昔单抗vedotin,第1天静脉注射环磷酰胺750mg/m2,第1天静脉注射多柔比星50mg/m2,第1-3天每天静脉注射依托泊苷100mg/m2,并在第1-5天每天口服泼尼松100mg)与预防性G-CSF。对治疗有反应的患者可以在自体造血干细胞移植(HSCT)后或在CHEP-BV后直接接受本妥昔单抗维多汀巩固多达十个周期。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中本妥昔单抗vedotin的推荐2期剂量)的参与者的3+3安全性引入期间的不可接受的毒性,以及接受研究治疗并进行反应评估的参与者的CHEP-BV诱导治疗后的完全缓解率。该研究已在ClinicalTrials.gov(NCT03113500)注册,这个队列完成了试验。该试验正在进行中,招募了一个新的队列。
结果:54例患者被筛选为合格,48例患者被纳入研究。参与者(18[38%]女性和30[63%]男性;34[71%]白人,四个[8%]黑色,五个[10%]亚洲人,十个[21%]西班牙裔,和37[77%]非西班牙裔人)在2017年12月4日至2021年6月14日之间招募和登记,并随访至2023年8月25日,数据库被锁定进行分析。48名参与者可评估毒性,47人的反应可评估(1名参与者在反应评估前死于COVID-19).在安全导入期间,六个参与者中的一个有不可接受的毒性(即,在广泛骨髓受累的参与者中,血小板计数<10000/mm3),并证实了CHEP-BV中建议的2期剂量为1·8mg/kg本妥昔单抗vedotin。在CHEP-BV完成时,47名参与者中有37名完全回应,完全缓解率为79%(95%CI64-89)。最常见的3级或更高的CHEP-BV相关毒性是中性粒细胞减少症(48个中的14个[29%]),白细胞减少症(11[23%]),贫血(十[21%]),发热性中性粒细胞减少症(十[21%]),淋巴细胞减少(九[19%]),和血小板减少症(9[19%])。没有治疗相关的死亡。
结论:在非间变性大细胞淋巴瘤以外的主要表达CD30的外周T细胞淋巴瘤患者中,CHEP-BV(有或没有自体HSCT),然后进行本妥昔单抗维多汀巩固是安全且活跃的。
背景: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的国家癌症研究所。
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.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: SeaGen, Leukemia and Lymphoma Society, Lymphoma Research Foundation, and the National Cancer Institute of the National Institutes of Health.