Youn H Kim1, Mahkam Tavallaee2, Uma Sundram2, Katrin A Salva2, Gary S Wood2, Shufeng Li2, Sima Rozati2, Seema Nagpal2, Michael Krathen2, Sunil Reddy2, Richard T Hoppe2, Annie Nguyen-Lin2, Wen-Kai Weng2, Randall Armstrong2, Melissa Pulitzer2, Ranjana H Advani2, Steven M Horwitz2. 1. Youn H. Kim, Mahkam Tavallaee, Uma Sundram, Shufeng Li, Sima Rozati, Seema Nagpal, Michael Krathen, Sunil Reddy, Richard T. Hoppe, Annie Nguyen-Lin, Wen-Kai Weng, Randall Armstrong, and Ranjana H. Advani, Stanford University, Stanford, CA; Katrin A. Salva and Gary S. Wood, University of Wisconsin and William S. Middleton Memorial Veterans Hospital, Madison, WI; and Melissa Pulitzer and Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY. younkim@stanford.edu. 2. Youn H. Kim, Mahkam Tavallaee, Uma Sundram, Shufeng Li, Sima Rozati, Seema Nagpal, Michael Krathen, Sunil Reddy, Richard T. Hoppe, Annie Nguyen-Lin, Wen-Kai Weng, Randall Armstrong, and Ranjana H. Advani, Stanford University, Stanford, CA; Katrin A. Salva and Gary S. Wood, University of Wisconsin and William S. Middleton Memorial Veterans Hospital, Madison, WI; and Melissa Pulitzer and Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY.
Abstract
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 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.
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 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.
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