Universität zu Köln

Boumaza, Xavier ORCID: 0000-0001-7618-3585, Bonneau, Baptiste, Roos-Weil, Damien, Pinnetti, Carmela, Rauer, Sebastian, Nitsch, Louisa, Del Bello, Arnaud, Jelcic, Ilijas, Suehs, Kurt-Wolfram, Gasnault, Jacques, Goreci, Yasemin, Grauer, Oliver, Gnanapavan, Sharmilee, Wicklein, Rebecca, Lambert, Nicolas, Perpoint, Thomas, Beudel, Martijn, Clifford, David, Sommet, Agnes, Cortese, Irene and Martin-Blondel, Guillaume (2023). Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors. Ann. Neurol., 93 (2). S. 257 - 271. HOBOKEN: WILEY. ISSN 1531-8249

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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conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add-on to standard of care.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 2022

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Boumaza, Xavier UNSPECIFIED orcid.org/0000-0001-7618-3585 UNSPECIFIED Bonneau, Baptiste UNSPECIFIED UNSPECIFIED UNSPECIFIED Roos-Weil, Damien UNSPECIFIED UNSPECIFIED UNSPECIFIED Pinnetti, Carmela UNSPECIFIED UNSPECIFIED UNSPECIFIED Rauer, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Nitsch, Louisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Del Bello, Arnaud UNSPECIFIED UNSPECIFIED UNSPECIFIED Jelcic, Ilijas UNSPECIFIED UNSPECIFIED UNSPECIFIED Suehs, Kurt-Wolfram UNSPECIFIED UNSPECIFIED UNSPECIFIED Gasnault, Jacques UNSPECIFIED UNSPECIFIED UNSPECIFIED Goreci, Yasemin UNSPECIFIED UNSPECIFIED UNSPECIFIED Grauer, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Gnanapavan, Sharmilee UNSPECIFIED UNSPECIFIED UNSPECIFIED Wicklein, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Lambert, Nicolas UNSPECIFIED UNSPECIFIED UNSPECIFIED Perpoint, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Beudel, Martijn UNSPECIFIED UNSPECIFIED UNSPECIFIED Clifford, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Sommet, Agnes UNSPECIFIED UNSPECIFIED UNSPECIFIED Cortese, Irene UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin-Blondel, Guillaume UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-697732
DOI:	10.1002/ana.26512
Journal or Publication Title:	Ann. Neurol.
Volume:	93
Number:	2
Page Range:	S. 257 - 271
Date:	2023
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1531-8249
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RECONSTITUTION INFLAMMATORY SYNDROME; T-CELL RESPONSES; JC VIRUS; CEREBROSPINAL-FLUID; ANTIRETROVIRAL THERAPY; HIV-INFECTION; PML; LYMPHOCYTES; SURVIVAL; CD4(+) Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69773