Damien Roos-Weil1, Nicolas Weiss2,3, Amélie Guihot4, Madalina Uzunov5, Agnès Bellanger6, Bruno Eymard7, David Saadoun8, Caroline Houillier9, Ahmed Idbaih9, Sophie Demeret2, Claire Deback10,11, Véronique Leblond5, Damien Galanaud12, Natalia Shor12, Valérie Pourcher13. 1. Sorbonne Université, Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, APHP, 47-83 Bd de l'Hôpital, 75651, Paris Cedex, France. damien.roosweil@aphp.fr. 2. Sorbonne Université, AP-HP, Hôpital de la Pitié-Salpêtrière, Département de Neurologie, Unité de Médecine Intensive Réanimation Neurologique, and Institut du Cerveau et de la Moelle Épinière, ICM, F-75013, Paris, France. 3. Inserm U1127, CNRS UMR 7225, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et Fibro-Inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), F-75013, Paris, France. 4. Sorbonne UniversitéAssistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-SalpêtrièreInserm U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Département d'Immunologie, Paris, France. 5. Sorbonne Université, Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, APHP, 47-83 Bd de l'Hôpital, 75651, Paris Cedex, France. 6. Pharmacie à Usage Intérieur, Sorbonne Université, AP-HP, Hôpital Pitié-Salpêtrière, APHP, Paris, France. 7. Nord-Est/Ile-de-France Neuromuscular Reference Center, Myology Institute, Pitié-Salpêtrière Hospital, Paris, France. 8. Department of Internal Medicine and Clinical Immunology, Centre National de Références Maladies Autoimmunes Systémiques Rares, Centre National de Références Maladies Autoinflammatoires Rares et Amyloses Inflammatoires, Sorbonne Université, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France. 9. CNRS, UMR S 1127, Institut du Cerveau et de la Moelle Épinière, ICM, Sorbonne Université, Inserm, AP-HPHôpitaux Universitaires la Pitié Salpêtrière, Charles Foix, Service de Neurologie 2-Mazarin, F-75013, Paris, France. 10. Laboratoire de Virologie, AP-HP, Hôpitaux Universitaires Paris Sud Saclay, Hôpital Paul Brousse, Villejuif, France. 11. Inserm, Inflammation, Microbiome and Immunosurveillance, Université Paris-Saclay, Clamart, France. 12. Department of Neuroradiology, Sorbonne Université, Pitié Salpêtrière Hospital, APHP, Paris, France. 13. Sorbonne Université, AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière Charles Foix, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Service de Maladies Infectieuses et Tropicales, INSERM 1136, 47-83 Bd de l'Hôpital, 75651, Paris Cedex, France. valerie.martinez@aphp.fr.
Abstract
OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) is a very rare and opportunistic encephalitis caused by JC polyomavirus that is linked to profound immunosuppression and is usually fatal unless immune function can be restored. Immune checkpoint inhibitors (ICI) are monoclonal antibodies (mAbs) that block either CTLA-4 or PD-1 inhibitor receptors, thus enhancing antiviral T-cell activity. Successful treatment of PML by ICI has recently generated some enthusiasm in case reports/small series of patients. However, the initial enthusiasm was mitigated by some individual case reports that did not show any benefit. More data are thus warranted about efficacy of immune checkpoint inhibitors in the specific context of PML. METHODS AND RESULTS: We report here the outcomes of six PML patients treated by ICI between 2017 and 2019. Underlying causes of immunosuppression consisted in hematologic malignancies (n = 4), primary immune deficiency (n = 1) and use of immunosuppressive therapies for myasthenia gravis (n = 1). Three patients were alive with a mean follow-up of 21 months (14-33) after first ICI infusion, including one patient with frank clinical response, one with stabilization, and one with initial worsening and further stabilization of PML. The three other patients rapidly died from PML. CONCLUSIONS: Our data suggest that ICI may be effective for PML treatment but were less impressive than the ones previously reported. Larger studies are thus warranted to confirm this efficacy and to identify the predictive factors of response.
OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) is a very rare and opportunistic encephalitis caused by JC polyomavirus that is linked to profound immunosuppression and is usually fatal unless immune function can be restored. Immune checkpoint inhibitors (ICI) are monoclonal antibodies (mAbs) that block either CTLA-4 or PD-1 inhibitor receptors, thus enhancing antiviral T-cell activity. Successful treatment of PML by ICI has recently generated some enthusiasm in case reports/small series of patients. However, the initial enthusiasm was mitigated by some individual case reports that did not show any benefit. More data are thus warranted about efficacy of immune checkpoint inhibitors in the specific context of PML. METHODS AND RESULTS: We report here the outcomes of six PML patients treated by ICI between 2017 and 2019. Underlying causes of immunosuppression consisted in hematologic malignancies (n = 4), primary immune deficiency (n = 1) and use of immunosuppressive therapies for myasthenia gravis (n = 1). Three patients were alive with a mean follow-up of 21 months (14-33) after first ICI infusion, including one patient with frank clinical response, one with stabilization, and one with initial worsening and further stabilization of PML. The three other patients rapidly died from PML. CONCLUSIONS: Our data suggest that ICI may be effective for PML treatment but were less impressive than the ones previously reported. Larger studies are thus warranted to confirm this efficacy and to identify the predictive factors of response.
Authors: L Nitsch; V Kaps; V Zschernack; N Gancarczyk; F van Essen; C Schmeel; T Klockgether; J Zimmermann; M Müller Journal: Nervenarzt Date: 2021-09-29 Impact factor: 1.297