PMID- 36151879
OWN - NLM
STAT- MEDLINE
DCOM- 20230130
LR  - 20230415
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Print)
IS  - 0364-5134 (Linking)
VI  - 93
IP  - 2
DP  - 2023 Feb
TI  - Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint 
      Inhibitors.
PG  - 257-270
LID - 10.1002/ana.26512 [doi]
AB  - 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      unpublished cases, who received immune checkpoint inhibitors as add-on to 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.
CI  - (c) 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on 
      behalf of American Neurological Association.
FAU - Boumaza, Xavier
AU  - Boumaza X
AUID- ORCID: 0000-0001-7618-3585
AD  - Department of Infectious and Tropical Diseases, Toulouse University Hospital, 
      Toulouse, France.
FAU - Bonneau, Baptiste
AU  - Bonneau B
AD  - Department of Medical Pharmacology, CIC 1436, Toulouse University Hospital, 
      Toulouse, France.
FAU - Roos-Weil, Damien
AU  - Roos-Weil D
AD  - Department of Hematology, Pitie-Salpetriere Hospital, Sorbonne University, Paris, 
      France.
FAU - Pinnetti, Carmela
AU  - Pinnetti C
AD  - HIV/AIDS Clinical Unit, National Institute for Infectious Disease "L. 
      Spallanzani", Rome, Italy.
FAU - Rauer, Sebastian
AU  - Rauer S
AD  - Department of Neurology, Medical Center, University of Freiburg, Freiburg, 
      Germany.
FAU - Nitsch, Louisa
AU  - Nitsch L
AD  - Department of Neurology, University Hospital Bonn, Bonn, Germany.
FAU - Del Bello, Arnaud
AU  - Del Bello A
AD  - Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, 
      France.
AD  - Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM 
      UMR1291, CNRS UMR5051, Toulouse III University, Toulouse, France.
FAU - Jelcic, Ilijas
AU  - Jelcic I
AD  - Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, 
      University Hospital Zurich and University of Zurich, Zurich, Switzerland.
FAU - Suhs, Kurt-Wolfram
AU  - Suhs KW
AD  - Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover 
      Medical School, Hannover, Germany.
FAU - Gasnault, Jacques
AU  - Gasnault J
AD  - Unit of Rehabilitation of Neuroviral Diseases, Bicetre Hospital, APHP, Le 
      Kremlin-Bicetre, France.
AD  - INSERM U1186, Paul Brousse Hospital, Paris Saclay University, Villejuif, France.
FAU - Goreci, Yasemin
AU  - Goreci Y
AD  - Department of Neurology, University Hospital of Cologne, Cologne, Germany.
FAU - Grauer, Oliver
AU  - Grauer O
AD  - Department of Neurology, Institute of Translational Neurology, University 
      Hospital Munster, Munster, Germany.
FAU - Gnanapavan, Sharmilee
AU  - Gnanapavan S
AD  - Department of Neurology, Barts Health NHS Trust and Queen Mary University of 
      London, London, UK.
FAU - Wicklein, Rebecca
AU  - Wicklein R
AUID- ORCID: 0000-0002-6661-6081
AD  - Department of Neurology, Technical University of Munich, Munich, Germany.
FAU - Lambert, Nicolas
AU  - Lambert N
AUID- ORCID: 0000-0002-6660-0100
AD  - Department of Neurology, University Hospital of Liege, Liege, Belgium.
FAU - Perpoint, Thomas
AU  - Perpoint T
AD  - Department of Infectious and Tropical Diseases, Lyon University Hospital, Lyon, 
      France.
FAU - Beudel, Martijn
AU  - Beudel M
AD  - Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the 
      Netherlands.
AD  - Department of Neuroscience, Amsterdam University Medical Center, Amsterdam, the 
      Netherlands.
FAU - Clifford, David
AU  - Clifford D
AD  - Department of Neurology, Washington University in St Louis, St Louis, MO, USA.
FAU - Sommet, Agnes
AU  - Sommet A
AD  - Department of Medical Pharmacology, CIC 1436, Toulouse University Hospital, 
      Toulouse, France.
FAU - Cortese, Irene
AU  - Cortese I
AD  - Experimental Immunotherapeutics Unit, National Institute of Neurological 
      Disorders and Stroke, Bethesda, MD.
FAU - Martin-Blondel, Guillaume
AU  - Martin-Blondel G
AUID- ORCID: 0000-0002-8363-7028
AD  - Department of Infectious and Tropical Diseases, Toulouse University Hospital, 
      Toulouse, France.
AD  - Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM 
      UMR1291, CNRS UMR5051, Toulouse III University, Toulouse, France.
AD  - European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study 
      Group on Infections of the Brain (ESGIB), Basel, Switzerland.
CN  - Immunotherapy for PML Study Group
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20221017
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Humans
MH  - *Leukoencephalopathy, Progressive Multifocal/drug therapy
MH  - Immune Checkpoint Inhibitors/adverse effects
MH  - Retrospective Studies
MH  - *JC Virus
MH  - *Immune Reconstitution Inflammatory Syndrome/drug therapy
PMC - PMC10092874
COIS- Nothing to report.
FIR - Grimbacher, Bodo
IR  - Grimbacher B
FIR - Warnke, Clemens
IR  - Warnke C
FIR - Wicklein, Rebecca
IR  - Wicklein R
FIR - Wijburg, Martijn
IR  - Wijburg M
FIR - Brouwer, Matthijs
IR  - Brouwer M
FIR - Lambert, Nicolas
IR  - Lambert N
FIR - Engalenc, Xavier
IR  - Engalenc X
FIR - Gaudin, Marion
IR  - Gaudin M
FIR - Kupper, Clemens
IR  - Kupper C
FIR - Aouba, Achille
IR  - Aouba A
FIR - Manda, Victoria
IR  - Manda V
FIR - Brousse, Xavier
IR  - Brousse X
FIR - Ducours, Mailys
IR  - Ducours M
FIR - Duffau, Pierre
IR  - Duffau P
FIR - Ouallet, Jean-Christophe
IR  - Ouallet J
FIR - Mrabet, Hela
IR  - Mrabet H
FIR - Gourdon, Florence
IR  - Gourdon F
FIR - Le Marechal, Marion
IR  - Le Marechal M
FIR - Bernard-Valnet, Raphael
IR  - Bernard-Valnet R
FIR - Delobel, Pierre
IR  - Delobel P
FIR - Lajaunie, Rebecca
IR  - Lajaunie R
FIR - Treiner, Emmanuel
IR  - Treiner E
FIR - Lhomme, Sebastien
IR  - Lhomme S
FIR - Bonneville, Fabrice
IR  - Bonneville F
FIR - Ribaute, Carole
IR  - Ribaute C
FIR - Ciron, Jonathan
IR  - Ciron J
FIR - Biotti, Damien
IR  - Biotti D
FIR - Kamar, Nassim
IR  - Kamar N
FIR - Weiss, Nicolas
IR  - Weiss N
FIR - Pourcher, Valerie
IR  - Pourcher V
FIR - Rakotoarison, Juliette
IR  - Rakotoarison J
FIR - Leveneur, Yann
IR  - Leveneur Y
FIR - De Menibus, Laurence
IR  - De Menibus L
FIR - Grassl, Niklas
IR  - Grassl N
FIR - Lifermann, Francois
IR  - Lifermann F
FIR - Cohen-Aubart, Fleur
IR  - Cohen-Aubart F
FIR - Ney, Douglas
IR  - Ney D
FIR - Kapadia, Ronak
IR  - Kapadia R
FIR - Dinur-Schejter, Yael
IR  - Dinur-Schejter Y
FIR - Shifman, Tzlil
IR  - Shifman T
FIR - Shamriz, Oded
IR  - Shamriz O
FIR - Berger, Joseph
IR  - Berger J
FIR - Lambotte, Olivier
IR  - Lambotte O
FIR - Perpoint, Thomas
IR  - Perpoint T
FIR - Harel, Asaff
IR  - Harel A
FIR - Wyplosz, Benjamin
IR  - Wyplosz B
EDAT- 2022/09/25 06:00
MHDA- 2023/01/31 06:00
PMCR- 2023/04/12
CRDT- 2022/09/24 04:33
PHST- 2022/09/01 00:00 [revised]
PHST- 2022/04/23 00:00 [received]
PHST- 2022/09/16 00:00 [accepted]
PHST- 2022/09/25 06:00 [pubmed]
PHST- 2023/01/31 06:00 [medline]
PHST- 2022/09/24 04:33 [entrez]
PHST- 2023/04/12 00:00 [pmc-release]
AID - ANA26512 [pii]
AID - 10.1002/ana.26512 [doi]
PST - ppublish
SO  - Ann Neurol. 2023 Feb;93(2):257-270. doi: 10.1002/ana.26512. Epub 2022 Oct 17.