Outcome of Progressive Multifocal Leukoencephalopathy Treated by Interleukin‐7

Rébecca Lajaunie (1) , Ilaria Mainardi (2) , Jacques Gasnault (3) , Vanessa Rousseau (4) , Andrea Tarantino , Agnès Sommet (4) , Paola Cinque (2) , Guillaume Martin-Blondel (5, 1) , Alexa Debard , Pierre Delobel , Nathalie Pansu , Cédric Gollion , Marie Benaiteau , Christine Jacomet , Nicolas Mélé , Antoine Moulignier , Felipe Suarez , Yvon Ruch , Christine Tranchant , Adrien Lemaignen , Sophie Langner-Lemercier , Rodolphe Buzele , Aurelien Guffroy , Cécile Moluçon-Chabrot , Pierre Tattevin (6, 7) , Giovanna Melica , Carmen‐ionela Badiu , Chrystel Cheraud-Bonfort , Anne Salmon , Karl Bjornar Alstadhaug , F. Matthew Kuhlmann , Lucas Gorza , Adrien Wang , Heidi Wille , Elodie Curlier , Mojgan Hessamfar , Florent Valour , Thomas Perpoint , Igor Koralnik , Kevin Decaestecker , William Vindrios , Anne Guilbert , Jean Marc Boulesteix , Sylvie Colin De Verdière , Antoine Roux , Amila Patel , Michelle Fabian , Asaff Harel , Benjamin Wyplosz , Florence Ader

1 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
2 San Raffaele Scientific Institute
3 UMR 1186 - Immunologie intégrative des tumeurs
4 CIC 1436 - Centre d'investigation clinique de Toulouse
5 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
6 CHU Pontchaillou [Rennes]
7 BRM - ARN régulateurs bactériens et médecine

Objective: Restoring anti-JC virus (JCV) immunity is the only treatment of progressive multifocal leukoencephalopathy (PML). Interleukin-7 is a cytokine that increases number and function of T cells. We analyzed a population of PML patients who received recombinant human IL-7 (rhIL-7) to estimate survival and its determinants. Methods: After exclusion of patients with missing data or receiving other immunotherapies, findings from 64 patients with proven PML who received rhIL-7 between 2007 and 2020 were retrospectively analyzed. Logistic regression was used to analyze variables associated with one-year survival. Results: Underlying conditions were HIV/AIDS (n = 27, 42%), hematological malignancies (n = 16, 25%), primary immunodeficiencies (n = 13, 20%), solid organ transplantation (n = 4, 6%) and chronic inflammatory diseases (n = 4, 6%). One-year survival was 54.7% and did not differ by underlying condition. Survival was not associated with baseline characteristics, but with a >50% increase in blood lymphocytes (OR 4.1, 95%CI 1.2-14.9) and CD4+ T cells (OR 5.9, 95%CI 1.7-23.3), and a > 1 log copies/mL decrease in cerebrospinal fluid JCV DNA (OR 7.6, 95%CI 1.6-56.1) during the first month after rhIL-7 initiation. Side effects were mainly local and flu-like symptoms (n = 8, 12.5%) and PML-immune reconstitution inflammatory syndrome (IRIS) (n = 5, 8%). Interpretation: In this non-controlled retrospective study, survival did not differ from that expected in HIV/AIDS patients, but might have been improved in those with hematological malignancies, primary immunodeficiencies and transplant recipients. RhIL-7 might have contributed to the increase in blood lymphocytes and decrease in CSF JCV replication that were associated with better survival. ANN NEUROL 2022;91:496-505.

Domains: Life Sciences [q-bio]; Cancer

Rébecca Lajaunie, Ilaria Mainardi, Jacques Gasnault, Vanessa Rousseau, Andrea Tarantino, et al.. Outcome of Progressive Multifocal Leukoencephalopathy Treated by Interleukin‐7. Annals of Neurology, 2022, 91 (4), pp.496-505. ⟨10.1002/ana.26307⟩. ⟨hal-03780669⟩