Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project

作者：Youn H. Kim, Mahkam Tavallaee, Uma Sundram, Katrin A. Salva, Gary S. Wood, Shufeng Li, Sima Rozati, Seema Nagpal, Michael Krathen, Sunil Reddy, Richard T. Hoppe, Annie Nguyen-Lin, Wen-Kai Weng, Randall Armstrong, Melissa Pulitzer, Ranjana H. Advani, Sarah McCue Horwitz · 发表于：Journal of Clinical Oncology · 年份：2015 · DOI：10.1200/jco.2014.60.3969 · 被引用次数：283 · 研究领域：Cutaneous lymphoproliferative disorders research、Lymphoma Diagnosis and Treatment、Histiocytic Disorders and Treatments

PURPOSE: In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored. PATIENTS AND METHODS: In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety. RESULTS: Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event. CONCLUSION: Brentuximab vedotin demonstrated significant ...