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

Authors

  • Kenneth R. Carson MD,

    Corresponding author
    1. Division of Medical Oncology, Washington University School of Medicine, St Louis, Missouri
    • Corresponding author: Kenneth R. Carson, MD, Division of Oncology, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8056, St. Louis, MO 63110; Fax: (314) 747-5123; kcarson@dom.wustl.edu

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    • The first 2 authors contributed equally to this article.

  • Scott D. Newsome DO,

    1. Division of Neuroimmunology and Neuroinfectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland
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    • The first 2 authors contributed equally to this article.

  • Ellen J. Kim MD,

    1. Division of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
    2. Division of Medical Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Nina D. Wagner-Johnston MD,

    1. Division of Medical Oncology, Washington University School of Medicine, St Louis, Missouri
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  • Gloria von Geldern MD,

    1. Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland
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  • Craig H. Moskowitz MD,

    1. Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Alison J. Moskowitz MD,

    1. Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Alain H. Rook MD,

    1. Division of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
    2. Division of Medical Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Pankaj Jalan MD,

    1. Division of Neurology, Southern Illinois College of Medicine, Springfield, Illinois
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  • Alison W. Loren MD,

    1. Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Daniel Landsburg MD,

    1. Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Thomas Coyne MD,

    1. Department of Pathology and Laboratory Medicine, Robert Wood Johnson School of Medicine, Rutgers University, Piscataway, New Jersey
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  • Donald Tsai MD,

    1. Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Dennis W. Raisch PhD,

    1. University of New Mexico College of Pharmacy, VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico
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  • LeAnn B. Norris PharmD,

    1. Southern Network on Adverse Reactions (SONAR) Program, South Carolina College of Pharmacy, Columbia, South Carolina
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  • P. Brandon Bookstaver PharmD,

    1. Southern Network on Adverse Reactions (SONAR) Program, South Carolina College of Pharmacy, Columbia, South Carolina
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  • Oliver Sartor MD,

    1. Division of Medical Oncology, Washington University School of Medicine, St Louis, Missouri
    2. Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana
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  • Charles L. Bennett MD

    1. Southern Network on Adverse Reactions (SONAR) Program, South Carolina College of Pharmacy, Columbia, South Carolina
    2. Arnold School of Public Health, University of South Carolina, Columbia, South Carolina
    3. Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina
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  • Critical review was provided by Eugene O. Major, PhD, chief of Laboratory of Molecular Medicine and Neuroscience at the National Institute of Neurologic Diseases of the National Institutes of Health in Bethesda, Maryland. Zaina Qureshi, PhD, MS; Brian Chen, PhD, JD; and Richard M. Schulz, PhD provided helpful critical review of the policy implications of the study.

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. Cancer 2014;120:2464–2471. © 2014 American Cancer Society.

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