Reply to Magnetic Resonance Imaging-Based Diagnosis of Progressive Multifocal Leukoencephalopathy in a Patient With Non-Hodgkin Lymphoma After Therapy With Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, and Rituximab

Disseminating timely information concerning serious adverse drug reactions is difficult. This is the mission of the Southern Network on Adverse Reactions (SONAR). Dima et al from Romania described a patient with non-Hodgkin lymphoma who was treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP-R regimen) who developed speech and motor dysfunction. Magnetic resonance imaging identified white matter defects. Cerebrospinal fluid (CSF) analysis did not identify JC virus (John Cunningham virus). An empirical diagnosis of rituximab-associated progressive multifocal leukoencephalopathy (PML) was made. Recently proposed PML diagnostic criteria from the Neuro-infectious Disease Section of the American Academy of Neurology require evidence of clinical disease progression, imaging, and JC virus (histopathologically or in the CSF).¹ If full criteria are not met, then alternative diagnoses need to be investigated. Access to relevant publications may not have been available in Romania, including our case series and review of PML.^2,3 The product label also does not report this information.⁴ Although >300 individuals with rituximab-associated PML have been reported to regulatory authorities, the label does not report this. The label also does not describe that in the setting of a suggestive magnetic resonance imaging scan and a negative CSF evaluation for JC virus, a second lumbar puncture or a brain biopsy should be considered. Finally, emerging data have identified a low baseline PML rate in patients with lymphoma, but a 5-fold increased rate in patients treated with rituximab and chemotherapy.⁵ We thank Dima et al for reporting this case, thereby reinforcing the observation that the most available source of safety information is the product label.