Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Abramson Cancer Center, Department of Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
JAMA Dermatol. 2021 Mar 1;157(3):317-321. doi: 10.1001/jamadermatol.2020.4901.
Treatment options for Sézary syndrome (SS) are limited and associated with low response rates. Brentuximab vedotin is a CD30-directed antibody-drug conjugate approved for refractory CD30-positive cutaneous T-cell lymphoma. However, limited data exist on its efficacy in SS, including in the pivotal phase 3 ALCANZA (A Phase 3 Trial of Brentuximab Vedotin (SGN-35) Versus Physician's Choice [Methotrexate or Bexarotene] in Participants With CD30-Positive Cutaneous T-Cell Lymphoma) trial.
To assess the preliminary efficacy and tolerability of brentuximab vedotin for SS.
DESIGN, SETTING, AND PARTICIPANTS: From January 1, 2017, to July 31, 2020, a total of 13 patients with SS received brentuximab vedotin and were analyzed as part of a retrospective case series. Median follow-up was 10.4 months (range, 1.4-34.6 months). All patients were 18 years or older with a diagnosis of SS and with B2 blood involvement at the time brentuximab vedotin therapy was initiated. This single-center study was conducted at a major academic referral center.
Intravenous brentuximab vedotin administration approximately every 3 weeks.
The primary end point was the global response rate. Outcomes were assessed in the skin and lymph nodes per the 2011 European Organization for Research and Treatment of Cancer-International Society of Cutaneous Lymphoma response criteria and in the blood per the 2018 Prospective Cutaneous Lymphoma International Prognostic Index revised blood response criteria.
The study included 13 patients (8 [62%] male; mean [SD] age, 68.2 [8.6] years). Of these 13 patients, 5 (38%) achieved a global response after a median of 6 cycles, including 1 complete response. Response rates by disease compartment were 38% in the skin, 63% in the blood, and 50% in the lymph nodes. Three of 11 patients (27%) with pruritus reported improvement. Skin CD30 positivity (>10%) was detected in 9 patients but was not associated with responses. Among responders, the median time to response was 6 weeks (range, 6-9 weeks), and the median duration of response was 5.5 months (range, 2.5-28.9 months). The median time to next treatment was 3.2 months (range, 1.5-36.7 months). Peripheral neuropathy occurred in 4 patients but resolved in 2 patients. Grade 2 adverse events were neuropathy (n = 2), constipation (n = 1), and hand-foot syndrome (n = 1).
In this case series, brentuximab vedotin use was associated with some efficacy in SS across multiple disease compartments and in the setting of refractory disease or low CD30 skin expression. Brentuximab vedotin may offer a manageable treatment schedule and low incidence of significant toxic effects.
Sézary 综合征 (SS) 的治疗选择有限，且应答率低。 Brentuximab vedotin 是一种针对 CD30 的抗体药物偶联物，已获批用于治疗难治性 CD30 阳性皮肤 T 细胞淋巴瘤。然而，关于其在 SS 中的疗效的数据有限，包括在关键的 3 期 ALCANZA（Brentuximab Vedotin（SGN-35）与医生选择的比较试验[甲氨蝶呤或贝沙罗汀]在 CD30 阳性皮肤 T 细胞淋巴瘤患者中的疗效）试验。
评估 Brentuximab vedotin 在 SS 中的初步疗效和耐受性。
设计、地点和参与者：从 2017 年 1 月 1 日至 2020 年 7 月 31 日，共有 13 例 SS 患者接受 Brentuximab vedotin 治疗，并作为回顾性病例系列的一部分进行分析。中位随访时间为 10.4 个月（范围，1.4-34.6 个月）。所有患者均为 18 岁或以上，在开始 Brentuximab vedotin 治疗时患有 SS 且 B2 血液受累。这项单中心研究在一家主要的学术转诊中心进行。
每 3 周静脉输注 Brentuximab vedotin。
主要终点是总体缓解率。根据 2011 年欧洲癌症研究与治疗组织-国际皮肤淋巴瘤学会反应标准评估皮肤和淋巴结的结果，根据 2018 年前瞻性皮肤淋巴瘤国际预后指数修订血液反应标准评估血液的结果。
研究纳入了 13 例患者（8 例[62%]为男性；平均[标准差]年龄为 68.2[8.6]岁）。这 13 例患者中，5 例（38%）在中位数为 6 个周期后达到了总体缓解，包括 1 例完全缓解。根据疾病部位，皮肤的缓解率为 38%，血液的缓解率为 63%，淋巴结的缓解率为 50%。11 例有瘙痒的患者中有 3 例（27%）报告有所改善。9 例患者皮肤 CD30 阳性（>10%），但与应答无关。在应答者中，应答时间中位数为 6 周（范围，6-9 周），应答持续时间中位数为 5.5 个月（范围，2.5-28.9 个月）。下一次治疗的中位时间为 3.2 个月（范围，1.5-36.7 个月）。4 例患者发生周围神经病变，但 2 例患者已缓解。2 级不良事件包括神经病变（n = 2）、便秘（n = 1）和手足综合征（n = 1）。
在本病例系列中，Brentuximab vedotin 在 SS 中多个疾病部位均显示出一定的疗效，且在难治性疾病或低 CD30 皮肤表达的情况下也有效。Brentuximab vedotin 可能提供可管理的治疗方案和较低的严重毒性事件发生率。
