Phase II investigator-initiated study of brentuximab vedotin in mycosis fungoides and Sézary syndrome with variable CD30 expression level: A multi-institution collaborative project Journal Article


Authors: Kim, Y. H.; Tavallaee, M.; Sundram, U.; Salva, K. A.; Wood, G. S.; Li, S. F.; Rozati, S.; Nagpal, S.; Krathen, M.; Reddy, S.; Hoppe, R. T.; Nguyen-Lin, A.; Weng, W. K.; Armstrong, R.; Pulitzer, M.; Advani, R. H.; Horwitz, S. M.
Article 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: Purpose In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Szary 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. (C) 2015 by American Society of Clinical Oncology
Keywords: survival; bortezomib; dexamethasone; amyloidosis; stem-cell transplantation; staging system; high-dose melphalan; light-chain amyloidosis; primary systemic; al amyloidosis; cardiac biomarkers
Journal Title: Journal of Clinical Oncology
Volume: 33
Issue: 32
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2015-11-10
Start Page: 3750
End Page: 3758
Language: English
ACCESSION: WOS:000366020100014
DOI: 10.1200/jco.2014.60.3969
PROVIDER: wos
PUBMED: 26195720
PMCID: PMC5089160
Notes: Article -- Source: Wos
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MSK Authors
  1. Melissa P Pulitzer
    126 Pulitzer
  2. Steven M Horwitz
    344 Horwitz