[en] ("[en] 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conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add-on to standard of care.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.","[en] ","")
Disciplines :
Neurology Immunology & infectious disease
Author, co-author :
Boumaza, Xavier ; Department of Infectious and Tropical Diseases, Toulouse University Hospital, Toulouse, France
Bonneau, Baptiste; Department of Medical Pharmacology, CIC 1436, Toulouse University Hospital, Toulouse, France
Roos-Weil, Damien; Department of Hematology, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
Pinnetti, Carmela; HIV/AIDS Clinical Unit, National Institute for Infectious Disease "L. Spallanzani", Rome, Italy
Rauer, Sebastian; Department of Neurology, Medical Center, University of Freiburg, Freiburg, Germany
Nitsch, Louisa; Department of Neurology, University Hospital Bonn, Bonn, Germany
Del Bello, Arnaud; Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France ; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291, CNRS UMR5051, Toulouse III University, Toulouse, France
Jelcic, Ilijas; Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
Sühs, Kurt-Wolfram; Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany
Gasnault, Jacques; Unit of Rehabilitation of Neuroviral Diseases, Bicêtre Hospital, APHP, Le Kremlin-Bicêtre, France ; INSERM U1186, Paul Brousse Hospital, Paris Saclay University, Villejuif, France
Goreci, Yasemin; Department of Neurology, University Hospital of Cologne, Cologne, Germany
Grauer, Oliver; Department of Neurology, Institute of Translational Neurology, University Hospital Münster, Münster, Germany
Gnanapavan, Sharmilee; Department of Neurology, Barts Health NHS Trust and Queen Mary University of London, London, UK
Wicklein, Rebecca ; Department of Neurology, Technical University of Munich, Munich, Germany
Lambert, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > > Service de neurologie
Perpoint, Thomas; Department of Infectious and Tropical Diseases, Lyon University Hospital, Lyon, France
Beudel, Martijn; Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands ; Department of Neuroscience, Amsterdam University Medical Center, Amsterdam, the Netherlands
Clifford, David; Department of Neurology, Washington University in St Louis, St Louis, MO, USA
Sommet, Agnès; Department of Medical Pharmacology, CIC 1436, Toulouse University Hospital, Toulouse, France
Cortese, Irene; Experimental Immunotherapeutics Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD
Martin-Blondel, Guillaume ; Department of Infectious and Tropical Diseases, Toulouse University Hospital, Toulouse, France ; Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291, CNRS UMR5051, Toulouse III University, Toulouse, France ; European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Infections of the Brain (ESGIB), Basel, Switzerland
NINDS - National Institute of Neurological Disorders and Stroke
Funding text :
We thank patients and their relatives, and caring nurses and physicians. This study was not funded. I.C. is supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program.
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