By Hai H. Hoang, MD
Assistant Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system caused by the reactivation of the JC virus. The authors of this study conducted a multi-centered retrospective observational study on 64 patients with PML who were treated with recombinant human IL-7 (RhIL-7). Overall, the one-year all-cause survival following start of RhIL-7 was 55% and similar among human immunodeficiency virus/acquired immunodeficiency syndrome, hematological malignancies, and primary immunodeficiencies.
SOURCE: Lajaunie R, Mainardi I, Gasnault J, et al. Outcome of progressive multifocal leukoencephalopathy treated by interleukin-7. Ann Neurol 2022;91:496-505.
Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by the reactivation of the JC virus (JCV) in hosts with impaired cellular immunity (innate immune system). Since there is no antiviral drug known to be active against JCV, recovery of the immune system’s antiviral response remains, to date, the only alternative to control PML.
Emerging evidence suggests PML remission can be achieved with novel immunotherapeutic approaches that promote the recovery anti-JCV immune responses, including immune checkpoint blockade, adoptive transfer of anti-polyomavirus specific T cells, and use of filgrastim or cytokines, including interleukin-7 (IL-7). IL-7 is a cytokine that is pivotal in regulating peripheral naïve T cell survival and homeostasis. Recombinant human IL-7 (RhIL-7) is a glycosylated protein synthesized by genetically engineered cell lines.
Lajaunie et al performed a retrospective multicenter study aimed at looking at the 12-month survival rates of patients with PML after RhIL-7 initiation. The study evaluated patients from 2007-2020 at multiple hospitals in France. Sixty-four of the 85 eligible patients receiving RhIL-7 were included in the study. Underlying diseases in the patients were 42% with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), 25% with hematological malignancies, 20% with primary immunodeficiencies, 6% with solid organ transplantation, and 6% with chronic inflammatory diseases.
There were no significant differences in the cerebrospinal fluid (CSF) JCV polymerase chain reaction load among the groups. Administration of RhIL-7 was at a dosage of 10 µg/kg/injection in 86% of patients and 20 µg/kg/injection in 14% of patients, and most patients (88%) received three or more injections. All patients with HIV/AIDS received optimized combined anti-retroviral therapy following PML diagnosis with control of HIV-1 replications in all except one patient.
One-year survival following the start of RhIL-7 was 55% and was similar among patients with HIV/AIDS, hematological malignancies, and primary immunodeficiencies. Survival was associated with > 50% increase in blood lymphocytes and a statistically significant reduction in JCV deoxyribonucleic acid in patients’ CSF during the first month of treatment with IL-7. Thirty percent of treated patients reported side effects, mostly consisting of local injection reactions and flu-like symptoms (40%). PML immune reconstitution inflammatory syndrome was diagnosed in 8% and was associated with clinical worsening with median increase in Modified Rankin Scale score of 1.
The authors concluded that the administration of RhIL-7 in patients with PML seems to have a beneficial effect in patients with hematological malignancies, primary immune deficits, and transplant recipients. Quantitatively, CD4 T cell count increased and CSF JCV replication decreased during the treatment, but it was not possible to ascertain whether they depended on RhIL-7 therapy, immune restoration through combined anti-retroviral therapy, withdrawal of immunosuppressive drugs, or a combination.
Limitations of this study include its observational, retrospective, and non-comparative design and inability to control for confounding variables, such as additional treatments with the RhIL-7 medication. Overall, this study presents a promising therapy for a neurologic disease with very few treatment options. Future studies should focus on a prospective study with an age- and sex-matched control to truly determine the efficacy