Virus-Specific T Cells and Response to Checkpoint Inhibitors in Progressive Multifocal Leukoencephalopathy.

Möhn N; Grote-Levi L; Bonifacius A; Tischer-Zimmermann S; Nay S; Jendretzky KF; Sassmann ML; Karacondi K; Zent M; Konen FF; Sühs KW; Meuth SG; Pawlitzki M; Warnke C; Ayzenberg I; Schneider R; Helmchen C; Brüggemann N; Klebe S; Hildner M; Grefkes C; Nitsch L; Hühnchen P; Böltz S; Alt L; Tumani H; Kleinschnitz C; Pul R; Grauer O; Clifford D; Gnanapavan S; Wicklein R; Perpoint T; Beudel M; Del Bello A; Rauer S; Wiendl H; Jelcic I; Gasnault J; Cimini E; Antinori A; Pinnetti C; Pourcher V; Weiss N; Lambert N; Maecker-Kolhoff B; Höglinger GU; Zahraeifard S; Cortese I; Eiz-Vesper B; Martin-Blondel G; Skripuletz T; Immunotherapy for PML Study Group

Zusammenfassung

IMPORTANCE - OBJECTIVE - DESIGN, SETTING, AND PARTICIPANTS - EXPOSURE - MAIN OUTCOME AND MEASURES - RESULTS - CONCLUSIONS AND RELEVANCE; Progressive multifocal leukoencephalopathy (PML) is a life-threatening demyelinating disease caused by reactivation of the JC virus (JCV) in immunocompromised patients. While immune checkpoint inhibitors (ICIs) show therapeutic potential, responses vary and predictive biomarkers are lacking.; To determine whether pretreatment JCV- and/or BK virus-specific T cells in the blood are associated with treatment efficacy.; This retrospective cohort study included 111 patients with PML who were treated with ICIs stratified by peripheral virus-specific T cell presence (ELISpot/flow cytometry) between August 2021 and May 2024, with a median (IQR) follow-up of 7 (1-13) months. Of 112 patients with definite PML across 39 centers, 1 patient refused participation; 111 patients were included.; Patients received pembrolizumab (n = 81), nivolumab (n = 28), or atezolizumab (n = 2) per availability and prescribing practices at participating centers.; Clinical outcomes, diagnostic parameters, and immune-related adverse events were compared; association of virus-specific T-cell responses with survival was analyzed using the Kaplan-Meier method.; The study cohort consisted of 111 patients (median [IQR] age, 61 [50-70] years; 74 male [66.6%]). Twenty-one patients had detectable virus-specific T cells prior to therapy, 22 were T cell-negative and 68 had an unknown T-cell status. T cell-positive patients showed significantly higher response rates and improved survival compared to both T cell-negative patients (18/21 [86%] vs 5/22 [23%]; P