Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis
Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis
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DOI：
10.1200/jco.2014.60.3787
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发表时间：
2015-11-10
影响因子：
45.3
通讯作者：
Talpur, Rakhshandra
中科院分区：
文献类型：
--
作者：
Duvic, Madeleine;Tetzlaff, Michael T.;Talpur, Rakhshandra
目的以CD30(+)受体为靶点，与单甲基金黄色E偶联的单抗(CAC10)--布妥昔单抗Vdotin。患者和方法48例CD30(+)淋巴组织增生性疾病或真菌病(MF)患者接受1.8 mg/kg的静脉滴注，每21天一次。结果48例可评价的患者(女性22例，男性26例；中位年龄59.5岁)总有效率73%(95%可信区间，60%~86%；48例患者中35例)，完全有效率35%(95%可信区间，22%~49%；48例患者中17例)。28例MF患者中有15例(54%；95%可信区间，31%至59%)有效，与CD30表达无关。在MF/Sezary综合征患者中，CD30低表达患者的总有效率为50%(5/10)，中等表达患者为58%(7/12)，高表达患者为50%(3/6)。起效时间12周(3~39周)，起效时间32周(3~93周)。淋巴瘤样丘疹(n=9)和原发皮肤间变性T细胞淋巴瘤(n=2)全部有效，有效时间3周(3~9周)，中位有效时间26周(6~44周)。完全应答者的可溶性基线CD30水平最低(P=0.036)。65%的患者出现1~2级周围神经病变(95%CI，52%~79%；48例患者中31例)，55%的患者(95%CI，41%~69%；31例患者中17例)仍在进行中，45%患者(95%CI，31%~59%；31例患者中14例)缓解，中位缓解时间为41.5周。中性粒细胞减少5例，恶心2例，胸痛2例，深静脉血栓形成1例，血透1例，脱水1例。剂量降至1.2 mg/kg是由于2级神经病变(n=6)、变态反应性炎症(n=1)、关节痛和疲劳(n=2)。结论布妥昔单抗维多丁治疗皮肤T细胞淋巴瘤和淋巴瘤样丘疹有效且耐受性良好，总有效率为73%，完全有效率为35%。(C)2015年度美国临床肿瘤学会
PurposeBrentuximab vedotin, a monoclonal antibody (cAC10) conjugated to monomethyl auristatin E, targets CD30(+) receptors. This phase II open-label trial was conducted to evaluate safety and efficacy in CD30(+) cutaneous T-cell lymphomas.Patients and MethodsForty-eight patients with CD30(+) lymphoproliferative disorders or mycosis fungoides (MF) received an infusion of 1.8 mg/kg every 21 days.ResultsForty-eight evaluable patients (22 women and 26 men; median age, 59.5 years) had an overall response rate of 73% (95% CI, 60% to 86%; 35 of 48 patients) and complete response rate of 35% (95% CI, 22% to 49%; 17 of 48 patients). Fifteen (54%; 95% CI, 31% to 59%) of 28 patients with MF responded, independent of CD30 expression. In patients with MF/Sezary syndrome, the overall response rate was 50% (five of 10 patients) in patients with low CD30 expression (< 10%), 58% (seven of 12 patients) in patients with medium expression (10% to 50%), and 50% (three of six patients) in patients with high expression (>= 50%). Time to response was 12 weeks (range, 3 to 39 weeks), and duration of response was 32 weeks (range, 3 to 93 weeks). All patients with lymphomatoid papulosis (n = 9) and primary cutaneous anaplastic T-cell lymphomas (n = 2) responded; time to response was 3 weeks (range, 3 to 9 weeks), and median duration of response was 26 weeks (range, 6 to 44 weeks). Soluble baseline CD30 levels were lowest in complete responders (P = .036). Grade 1 to 2 peripheral neuropathy was observed in 65% of patients (95% CI, 52% to 79%; 31 of 48 patients), is still ongoing in 55% of patients (95% CI, 41% to 69%; 17 of 31 patients), and resolved in 45% of patients (95% CI, 31% to 59%; 14 of 31 patients), with a median time to resolution of 41.5 weeks. Grade 3 to 4 events were neutropenia (n = 5), nausea (n = 2), chest pain (n = 2), deep vein thrombosis (n = 1), transaminitis (n = 1), and dehydration (n = 1). Dose reductions to 1.2 mg/kg were instituted as a result of grade 2 neuropathy (n = 6), transaminitis (n = 1), and arthralgias and fatigue (n = 2).ConclusionBrentuximab vedotin is both active and well tolerated in cutaneous T-cell lymphoma and lymphomatoid papulosis, with an overall response rate of 73% and complete response rate of 35%. (C) 2015 by American Society of Clinical Oncology