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Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project
Author(s) -
Carson Kenneth R.,
Newsome Scott D.,
Kim Ellen J.,
WagnerJohnston Nina D.,
Geldern Gloria,
Moskowitz Craig H.,
Moskowitz Alison J.,
Rook Alain H.,
Jalan Pankaj,
Loren Alison W.,
Landsburg Daniel,
Coyne Thomas,
Tsai Donald,
Raisch Dennis W.,
Norris LeAnn B.,
Bookstaver P. Brandon,
Sartor Oliver,
Bennett Charles L.
Publication year - 2014
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.28712
Subject(s) - medicine , progressive multifocal leukoencephalopathy , brentuximab vedotin , jc virus , primary central nervous system lymphoma , immune reconstitution inflammatory syndrome , leukoencephalopathy , hemiparesis , chemotherapy , magnetic resonance imaging , lymphoma , cd30 , radiology , immunology , multiple sclerosis , virus , viral load , angiography , antiretroviral therapy
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 .