Progressive Multifocal Leukoencephalopathy and Monoclonal Antibodies

Abstract

Progressive multifocal leukoencephalopathy (PML) is a viral infection predominantly seen in patients with HIV infection. However, with the increased use of monoclonal antibodies (MAB) for various lymphoproliferative disorders, we are now seeing this infection in non-HIV patients on drugs such as natalizumab, rituximab, and so on. The aim of this article is to review the relationship between the occurrence of PML and MAB used in the treatment of hematological malignancies and autoimmune diseases. Review of articles from PubMed-indexed journals which study PML in relation to the use of MAB. Relevant literature demonstrated an increased risk of reactivation of latent John Cunningham polyomavirus (JCV) resulting in development of PML in patients on long-term therapy with MAB. The highest incidence of 1 PML case per 1000 treated patients and 1 case per 32 000 was observed in patients treated with natalizumab and rituximab, respectively. Serological and polymerase chain reaction tests for the detection of JCV can be helpful in risk stratification of patients for the development of PML before and during therapy with MAB. Treatment with MAB can result in development of PML. Clinicians should include PML in differential diagnosis in patients treated with these agents if they manifest central nervous system symptoms.

Progressive Multifocal Leukoencephalopathy during Tocilizumab Treatment for Rheumatoid Arthritis

“…The virus remains latent in the kidneys, lymph nodes, and bone marrow, and relatively well-conserved JCV noncoding control regions (NCCRs) can be detected in the urine of asymptomatic healthy individuals ( 16 ). It has been suggested that the virus transforms into a neurotropic form by gene rearrangement after initial infection under immunocompromised conditions and replicates in glial cells ( 17 ). These NCCR sequences change over the course of active infection and are highly variable between PML patients ( 16 ).…”

“…These NCCR sequences change over the course of active infection and are highly variable between PML patients ( 16 ). The mechanisms underlying PML development during monoclonal antibody treatment are still poorly understood and may vary among biologic agents ( 2 , 17 ). However, it is suspected that the most important pathogenic mechanisms involved in PML evolution secondary to monoclonal antibody treatment include immunosuppression due to elimination/suppression of B cells, cytotoxic T cells, natural killer cells, and/or T helper cells ( 17 ).…”

Rituximab use in adult glomerulopathies and its rationale

“…In the above studies, none of the patients presented PML, but due to the high death rate, it is critical to keep in mind the possibility of developing PML. However, at this time there are no recommendations to screen patients for JCV 87 .…”

Epidemiological and molecular characterization of a novel adenovirus of squirrel monkeys after fatal infection during immunosuppression

“…Rituximab is also used off-label as an immunomodulatory therapy for renal transplant and other autoimmune disorders [22][23][24]. After more than 20 years of use, rituximab is considered a safe and effective immunomodulatory therapy; nevertheless, adverse events have been documented, most notably an increased risk of progressive multifocal leukoencephalopathy (PML) particularly for patients with haematological malignancies [25][26][27]. In contrast, reports of adenovirus disease in patients treated with rituximab are uncommon.…”