Abstract：
Brentuximab vedotin (BV), a conjugate of anti-CD30 antibody and monomethyl auristatin E, has emerged as a promising treatment option for refractory CD30+ mycosis fungoides (MF) and primary cutaneous anaplastic large-cell lymphoma (pcALCL). BV has been shown to be safe and effective in treating Hodgkin\'s lymphoma and peripheral T-cell lymphoma. This multicenter, prospective, single-arm phase I/II study evaluated the efficacy of BV in Japanese patients with CD30+ cutaneous lymphomas, namely CD30+ cutaneous T-cell lymphoma. Participants were divided into two groups: those with CD30+ MF or pcALCL (cohort 1, n = 13) and those with CD30+ lymphoproliferative disorders other than those in cohort 1 (cohort 2, n = 3). The studied population included the full analysis set (FAS), modified FAS (mFAS), and safety analysis set (SAF). These sets were identified in cohorts 1 and 1 + 2 and labeled FAS1 and FAS2, mFAS1 and mFAS2, and SAF1 and SAF2, respectively. Each treatment cycle lasted 3 weeks, and BV was continued for up to 16 cycles after the third cycle based on treatment response. The primary endpoint was the 4-month objective response rate (ORR4) determined by the Independent Review Forum (IRF). ORR4 was 69.2% for FAS1 and 62.5% for FAS2 (P < 0.0001). Secondary endpoints of ORR, assessed using the global response score (53.8% in FAS1) and modified severity-weighted assessment tool (62.5% in FAS1), using the IRF, provided results comparable to the primary findings. The incidence of ≥grade 3 adverse events (≥15%) in SAF1 was peripheral neuropathy in three patients (23%) and fever and eosinophilia in two patients (15%). In conclusion, BV showed favorable efficacy, tolerability, and safety profile in Japanese patients with relapsed or refractory CD30+ primary cutaneous T-cell lymphoma. The trial was registered with University Hospital Medical Information Network Clinical Trials Registry, Japan (protocol ID: UMIN000034205).
摘要：
Brentuximabvedotin(BV),抗CD30抗体和单甲基奥瑞他汀E的缀合物，已成为难治性CD30真菌病（MF）和原发性皮肤间变性大细胞淋巴瘤（pcALCL）的有希望的治疗选择。BV已被证明是安全和有效的治疗霍奇金淋巴瘤和外周T细胞淋巴瘤。这个多中心，prospective,单臂I/II期研究评估了BV在日本CD30+皮肤淋巴瘤患者中的疗效，即CD30+皮肤T细胞淋巴瘤。参与者分为两组：CD30MF或pcALCL患者（队列1，n=13）和除队列1以外的CD30淋巴增生性疾病患者（队列2，n=3）。研究人群包括完整的分析集(FAS)，改进的FAS(mFAS)，和安全分析集(SAF)。在队列1和1+2中鉴定这些组,分别标记为FAS1和FAS2、mFAS1和mFAS2以及SAF1和SAF2。每个治疗周期持续3周,根据治疗反应，在第三个周期后，BV持续多达16个周期。主要终点是独立审查论坛（IRF）确定的4个月客观缓解率（ORR4）。FAS1的ORR4为69.2%,FAS2为62.5%(P<0.0001)。ORR的次要终点，使用全球反应评分（FAS1中为53.8%）和改良的严重性加权评估工具（FAS1中为62.5%）进行评估，使用IRF，提供了与主要发现相当的结果。SAF1中≥3级不良事件（≥15％）的发生率为3例患者（23％）的周围神经病变和2例患者（15％）的发热和嗜酸性粒细胞增多。总之,BV显示出良好的疗效，耐受性,日本复发性或难治性CD30+原发性皮肤T细胞淋巴瘤患者的安全性和安全性。该试验已在大学医院医学信息网络临床试验登记处注册，日本（协议ID：UMIN000034205）。
