Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project.
Rituximab improves outcomes for persons with lymphoproliferative disorders and is increasingly used to treat immune-mediated illnesses. Recent reports describe 2 patients with systemic lupus erythematosus and 1 with rheumatoid arthritis who developed progressive multifocal leukoencephalopathy (PML) after rituximab treatment. We reviewed PML case descriptions among patients treated with rituximab from the Food and Drug Administration, the manufacturer, physicians, and a literature review from 1997 to 2008. Overall, 52 patients with lymphoproliferative disorders, 2 patients with systemic lupus erythematosus, 1 patient with rheumatoid arthritis, 1 patient with an idiopathic autoimmune pancytopenia, and 1 patient with immune thrombocytopenia developed PML after treatment with rituximab and other agents. Other treatments included hematopoietic stem cell transplantation (7 patients), purine analogs (26 patients), or alkylating agents (39 patients). One patient with an autoimmune hemolytic anemia developed PML after treatment with corticosteroids and rituximab, and 1 patient with an autoimmune pancytopenia developed PML after treatment with corticosteroids, azathioprine, and rituximab. Median time from last rituximab dose to PML diagnosis was 5.5 months. Median time to death after PML diagnosis was 2.0 months. The case-fatality rate was 90%. Awareness is needed of the potential for PML among rituximab-treated persons.
Carson
Kenneth R
KR
Siteman Comprehensive Cancer Center, Washington University School of Medicine, St Louis, MO, USA.
Evens
Andrew M
AM
Richey
Elizabeth A
EA
Habermann
Thomas M
TM
Focosi
Daniele
D
Seymour
John F
JF
Laubach
Jacob
J
Bawn
Susie D
SD
Gordon
Leo I
LI
Winter
Jane N
JN
Furman
Richard R
RR
Vose
Julie M
JM
Zelenetz
Andrew D
AD
Mamtani
Ronac
R
Raisch
Dennis W
DW
Dorshimer
Gary W
GW
Rosen
Steven T
ST
Muro
Kenji
K
Gottardi-Littell
Numa R
NR
Talley
Robert L
RL
Sartor
Oliver
O
Green
David
D
Major
Eugene O
EO
Bennett
Charles L
CL
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000009:adverse effects; D016903:Drug Monitoring / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D018023:HIV Seronegativity; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab