Progressive multifocal leukoencephalopathy treated by immune checkpoint inhibitors

Abstract: 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conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add-on to standard of care.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

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Annals of neurology. - 93, 2 (2023) , 257-270, ISSN: 1531-8249

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2022
• Urheber: Boumaza, Xavier ; Bonneau, Baptiste ; Roos‐Weil, Damien ; Pinnetti, Carmela ; Rauer, Sebastian ; Nitsch, Louisa ; Del Bello, Arnaud ; Jelcic, Ilijas ; Sühs, Kurt‐Wolfram ; Gasnault, Jacques ; Goreci, Yasemin ; Grauer, Oliver ; Gnanapavan, Sharmilee ; Wicklein, Rebecca ; Lambert, Nicolas ; Perpoint, Thomas ; Beudel, Martijn ; Clifford, David ; Sommet, Agnès ; Cortese, Irene ; Martin‐Blondel, Guillaume

Weitere Informationen

• DOI: 10.1002/ana.26512
• URN: urn:nbn:de:bsz:25-freidok-2305060
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 14.08.2025, 10:54 MESZ