Impact of Ocrelizumab Treatment on PML Risk Biomarkers

Background: John Cunningham virus (JCV) infection is highly prevalent and typically asymptomatic. Nevertheless, immunosuppressed patients may develop a severe opportunistic JCV brain infection resulting in a fatal disease called Progressive Multifocal Leukoencephalopathy (PML). Some Multiple Sclerosis (MS) disease-modifying treatments, such as natalizumab, carry a known risk of PML. Clinicians have the ability to gauge PML risk by evaluating a patient’s JCV antibody titer, with higher titers suggesting higher PML risk. Lymphopenia may also be a PML risk factor, especially if JCV titers are high. These biomarkers are used to avoid the risk of PML in MS patients. PML risk for MS patients receiving a newly approved anti-CD20 monoclonal antibody therapy, called ocrelizumab, has not yet been well established. As many patients are switching from other MS treatments to ocrelizumab, examining the impact of ocrelizumab on JCV indices and lymphocyte counts may be helpful to evaluate these patient’s PML risk. More assessment of the therapy’s impact on the results of, or the ability to utilize a tool such as a JCV antibody test is warranted.

Objectives: The aim of this study was to follow a cohort of MS patients treated at PennMedicine as they switched to ocrelizumab and assess how these patient’s JCV antibody titers and lymphocyte profiles fluctuated in response to the treatment change.

Methods: This is a retrospective review of medical records from patients treated at the PennMedicine Multiple Sclerosis Center. We compiled a database of patients who had recorded multiple previous JCV index values and lymphocyte profiles and followed them as they switched to ocrelizumab.

Results: Of the over 200 patients receiving ocrelizumab, over a quarter had previous JCV antibody tests. More than a third of these patients with prior JCV tests had at least one repeat JCV test after their first ocrelizumab infusion. Following the first treatment, JCV indexes rose by 0.047 (SD=0.181) on average. At least two patients in our cohort underwent JCV seroconversion after treatment change. As expected, ocrelizumab eradicated the CD19 B-cell population. CD3 Lymphocytes dropped on average by 254 cells/uL (SD=624 cells/uL) and the CD8 population dropped on average more than 90 cells/uL (SD=190 cells/uL) after ocrelizumab infusion.

Conclusions: After receiving ocrelizumab, patients on-average experienced a rise in JCV indices and a decline of B-cell populations. Further evaluation of this treatment’s long-term impact on PML risk is advised.