Purpose: Progressive multifocal leukoencephalopathy (PML) is a rare, fatal disease that results from activation of a highly prevalent, dormant John Cunningham (JC) virus—a variant of human polyomavirus—during immunosuppressed states. Rituximab, a CD20 monoclonal antibody immunomodulator, has been approved for non-Hodgkin lymphoma (NHL).
Methods: Using electronic medical records from the VA, ICD-9 codes were used to identify patients diagnosed with NHL, PML, and HIV within the VA from 2003 to 2011. Pharmacy records were used to identify patients receiving rituximab, cyclophosphamide, hydroxydaunorubicin, and vncristine. This project was conducted inside the Veterans Affairs Informatics and Computing Infrastructure after obtaining approvals from the VA IRB and other oversight groups.
Results: We identified 57,041 non-HIV NHL patients. A total of 14 out of 57,041 (0.025%) patients had developed PML; 7 out of 8,895 (7.8 per 10,000) were NHL patients who received rituximab subsequently developed PML; 7 out of 48,146 (1.5 per 10,000) were NHL patients who did not receive rituximab subsequently developed PML, which results in a statistically significant unadjusted relative risk of 5.4 (95% CI: 1.9 - 15.4) and an attributable risk of 6.3 per 10,000. Univariate analyses of other outcomes were not statistically significant between patients who received and those that did not receive rituximab.
Conclusions: These results show that among lymphoma patients, the use of rituximab is associated with a statistically significant relative risk for documented PML of 5.4. Measurement of JC virus prior to initiation of rituximab therapy as well as during rituximab therapy should be considered.