Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors

OBJECTIVE: Our aim was to assess the real‐world effectiveness of immune checkpoint inhibitors for treatment of patients with progressive multifocal leukoencephalopathy (PML). METHODS: We conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add‐on to standard of care. One‐year follow‐up data were analyzed to determine clinical outcomes and safety profile. Logistic regression was used to identify variables associated with 1‐year survival. RESULTS: Predisposing conditions included hematological malignancy (n = 38, 48.1%), primary immunodeficiency (n = 14, 17.7%), human immunodeficiency virus/acquired immunodeficiency syndrome (n = 12, 15.2%), inflammatory disease (n = 8, 10.1%), neoplasm (n = 5, 6.3%), and transplantation (n = 2, 2.5%). Pembrolizumab was most commonly used (n = 53, 67.1%). One‐year survival was 51.9% (41/79). PML–immune reconstitution inflammatory syndrome (IRIS) was reported in 15 of 79 patients (19%). Pretreatment expression of programmed cell death‐1 on circulating T cells did not differ between survivors and nonsurvivors. Development of contrast enhancement on follow‐up magnetic resonance imaging at least once during follow‐up (OR = 3.16, 95% confidence interval = 1.20–8.72, p = 0.02) was associated with 1‐year survival. Cerebrospinal fluid JC polyomavirus DNA load decreased significantly by 1‐month follow‐up in survivors compared to nonsurvivors (p < 0.0001). Thirty‐two adverse events occurred among 24 of 79 patients (30.4%), and led to treatment discontinuation in 7 of 24 patients (29.1%). INTERPRETATION: In this noncontrolled retrospective study of patients with PML who were treated with immune checkpoint inhibitors, mortality remains high. Development of inflammatory features or overt PML‐IRIS was commonly observed. This study highlights that use of immune checkpoint inhibitors should be strictly personalized toward characteristics of the individual PML patient. ANN NEUROL 2023;93:257–270