The first 2 authors contributed equally to this article.
Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project
Version of Record online: 25 APR 2014
© 2014 American Cancer Society
Volume 120, Issue 16, pages 2464–2471, August 15, 2014
How to Cite
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. and Bennett, C. L. (2014), Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project. Cancer, 120: 2464–2471. doi: 10.1002/cncr.28712
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.
- Issue online: 5 AUG 2014
- Version of Record online: 25 APR 2014
- Manuscript Accepted: 27 FEB 2014
- Manuscript Revised: 17 FEB 2014
- Manuscript Received: 28 OCT 2013
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.
Case information was obtained from clinicians (4 patients) or a US Food and Drug Administration database (1 patient).
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.
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.