title: Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Youn H
authors.initials: YH
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Mahkam
authors.initials: M
authors.lastname: Tavallaee
authors.affiliation: 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.
authors.forename: Uma
authors.initials: U
authors.lastname: Sundram
authors.affiliation: 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.
authors.forename: Katrin A
authors.initials: KA
authors.lastname: Salva
authors.affiliation: 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.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Wood
authors.affiliation: 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.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Sima
authors.initials: S
authors.lastname: Rozati
authors.affiliation: 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.
authors.forename: Seema
authors.initials: S
authors.lastname: Nagpal
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Krathen
authors.affiliation: 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.
authors.forename: Sunil
authors.initials: S
authors.lastname: Reddy
authors.affiliation: 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.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Hoppe
authors.affiliation: 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.
authors.forename: Annie
authors.initials: A
authors.lastname: Nguyen-Lin
authors.affiliation: 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.
authors.forename: Wen-Kai
authors.initials: WK
authors.lastname: Weng
authors.affiliation: 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.
authors.forename: Randall
authors.initials: R
authors.lastname: Armstrong
authors.affiliation: 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.
authors.forename: Melissa
authors.initials: M
authors.lastname: Pulitzer
authors.affiliation: 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.
authors.forename: Ranjana H
authors.initials: RH
authors.lastname: Advani
authors.affiliation: 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.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Horwitz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000079963:Brentuximab Vedotin; D016827:CD8 Antigens / Q000378:metabolism; D003299:Cooperative Behavior; D004334:Drug Administration Schedule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017730:Ki-1 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D012108:Research Personnel; D012307:Risk Factors; D012720:Severity of Illness Index; D012751:Sezary Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000098902:CD163 Antigen; D016827:CD8 Antigens; D018796:Immunoconjugates; D017730:Ki-1 Antigen; D011956:Receptors, Cell Surface; D000079963:Brentuximab Vedotin