Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: a report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project.
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.
Division of Medical Oncology, Washington University School of Medicine, St Louis, Missouri.
Kenneth R
KR
Carson
Scott D
SD
Newsome
Ellen J
EJ
Kim
Nina D
ND
Wagner-Johnston
Gloria
G
von Geldern
Craig H
CH
Moskowitz
Alison J
AJ
Moskowitz
Alain H
AH
Rook
Pankaj
P
Jalan
Alison W
AW
Loren
Daniel
D
Landsburg
Thomas
T
Coyne
Donald
D
Tsai
Dennis W
DW
Raisch
LeAnn B
LB
Norris
P Brandon
PB
Bookstaver
Oliver
O
Sartor
Charles L
CL
Bennett
D000328:Adult; D000368:Aged; D000079963:Brentuximab Vedotin; D006689:Hodgkin Disease / Q000188:drug therapy; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced*; D054446:Lymphoma, Primary Cutaneous Anaplastic Large Cell / Q000188:drug therapy; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy
D018796:Immunoconjugates; D000079963:Brentuximab Vedotin
autoimmune; brentuximab; fungoides; immunocompromised; lymphoma; vedotin