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

• Published in: Journal of clinical oncology Vol. 33; no. 32; pp. 3750 - 3758
• Main Authors: Kim, Youn H, Tavallaee, Mahkam, Sundram, Uma, Salva, Katrin A, Wood, Gary S, Li, Shufeng, Rozati, Sima, Nagpal, Seema, Krathen, Michael, Reddy, Sunil, Hoppe, Richard T, Nguyen-Lin, Annie, Weng, Wen-Kai, Armstrong, Randall, Pulitzer, Melissa, Advani, Ranjana H, Horwitz, Steven M
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 10.11.2015
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor - metabolism; CD8 Antigens - metabolism; Cooperative Behavior; Drug Administration Schedule; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoconjugates - administration & dosage; Immunoconjugates - adverse effects; Immunoconjugates - therapeutic use; Ki-1 Antigen - metabolism; Male; Middle Aged; Mycosis Fungoides - drug therapy; Mycosis Fungoides - metabolism; Mycosis Fungoides - pathology; Neoplasm Staging; ORIGINAL REPORTS; Prognosis; Receptors, Cell Surface - metabolism; Research Personnel; Risk Factors; Severity of Illness Index; Sezary Syndrome - drug therapy; Sezary Syndrome - metabolism; Sezary Syndrome - pathology; Skin Neoplasms - drug therapy; Skin Neoplasms - metabolism; Skin Neoplasms - pathology
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2014.60.3969

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. 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. 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. Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin.