Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project Journal Article


Authors: Carson, K. R.; Newsome, S. D.; Kim, E. J.; Wagner-Johnston, N. D.; Von Geldern, G.; Moskowitz, C. H.; Moskowitz, A. J.; Rook, A. H.; Jalan, P.; Loren, A. W.; Landsburg, D.; Coyne, T.; Tsai, D.; Raisch, D. W.; Norris, L. B.; Bookstaver, P. B.; Sartor, O.; Bennett, C. L.
Article Title: Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project
Abstract: BACKGROUND Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate that was approved in 2011 for the treatment of patients with anaplastic large cell and Hodgkin lymphomas. The product label indicates that 3 patients who were treated with BV developed progressive multifocal leukoencephalopathy (PML), a frequently fatal JC virus-induced central nervous system infection. Prior immunosuppressive therapy and compromised immune systems were postulated risk factors. In the current study, the authors reported 5 patients who developed BV-associated PML, including 2 immunocompetent patients. METHODS Case information was obtained from clinicians (4 patients) or a US Food and Drug Administration database (1 patient). RESULTS All 5 patients had lymphoid malignancies. Two patients with cutaneous T-cell lymphomas had not previously received chemotherapy. PML developed after a median of 3 BV doses (range, 2 doses-6 doses) and within a median of 7 weeks after BV initiation (range, 3 weeks-34 weeks). Presenting findings included aphasia, dysarthria, confusion, hemiparesis, and gait dysfunction; JC virus in the cerebrospinal fluid (2 patients) or central nervous system biopsy (3 patients); and brain magnetic resonance imaging scans with white matter abnormalities (5 patients). Four patients died at a median of 8 weeks (range, 6 weeks-16 weeks) after PML diagnosis. The sole survivor developed immune reconstitution inflammatory syndrome. CONCLUSIONS PML can develop after a few BV doses and within weeks of BV initiation. Clinicians should be aware of this syndrome, particularly when neurologic changes develop after the initiation of BV treatment. The decision to administer BV to patients with indolent cutaneous lymphomas should be based on consideration of risk-benefit profiles and of alternative options. © 2014 American Cancer Society.
Keywords: adult; clinical article; human tissue; aged; young adult; prednisone; salvage therapy; cisplatin; doxorubicin; cancer combination chemotherapy; drug withdrawal; alpha interferon; cytarabine; methotrexate; nuclear magnetic resonance imaging; carboplatin; dacarbazine; multiple cycle treatment; etoposide; peripheral neuropathy; autologous stem cell transplantation; chlormethine; ifosfamide; vinblastine; confusion; cutaneous t cell lymphoma; death; gamma interferon; lymphoma; bleomycin; methylprednisolone; progressive multifocal leukoencephalopathy; large cell lymphoma; corticosteroid; aphasia; navelbine; brain biopsy; amnesia; romidepsin; hemiparesis; mycosis fungoides; pralatrexate; classical hodgkin lymphoma; gait disorder; denileukin diftitox; dysarthria; bexarotene; autoimmune; immune reconstitution inflammatory syndrome; phototherapy; cerebrospinal fluid examination; brentuximab vedotin; immunocompromised; hemianopia; spinal cord biopsy; fungoides; human; male; female; priority journal; article; brentuximab; vedotin; jc virus
Journal Title: Cancer
Volume: 120
Issue: 16
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2014-08-15
Start Page: 2464
End Page: 2471
Language: English
DOI: 10.1002/cncr.28712
PROVIDER: scopus
PUBMED: 24771533
PMCID: PMC4460831
DOI/URL:
Notes: Export Date: 2 September 2014 -- CODEN: CANCA -- Source: Scopus
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MSK Authors
  1. Craig Moskowitz
    371 Moskowitz
  2. Alison Moskowitz
    141 Moskowitz