Co-occurrence of myositis and neuropathy after anti-CD30 therapy in a late-adolescent Hodgkin lymphoma patient

Abstract Objective Immune-related adverse events (irAEs) are recognized in oncology, particularly with immune checkpoint inhibitors and other targeted therapies. Brentuximab Vedotin (BV), is an anti-CD30 antibody–drug conjugate- its association with immune-mediated myositis remains unexplored. We re...

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Main Authors: Adela Della Marina, Lydia Rink, Andreas Hentschel, Michael M. Schündeln, Christopher Nelke, Heike Kölbel, Calvin Tucht, Vera Dobelmann, Tobias Ruck, Tim Hagenacker, Teresinha Evangelista, Ulrike Schara-Schmidt, Andreas Roos
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Language:English
Published: BMC 2025-06-01
Series:Acta Neuropathologica Communications
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Online Access:https://doi.org/10.1186/s40478-025-02056-2
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author Adela Della Marina
Lydia Rink
Andreas Hentschel
Michael M. Schündeln
Christopher Nelke
Heike Kölbel
Calvin Tucht
Vera Dobelmann
Tobias Ruck
Tim Hagenacker
Teresinha Evangelista
Ulrike Schara-Schmidt
Andreas Roos
author_facet Adela Della Marina
Lydia Rink
Andreas Hentschel
Michael M. Schündeln
Christopher Nelke
Heike Kölbel
Calvin Tucht
Vera Dobelmann
Tobias Ruck
Tim Hagenacker
Teresinha Evangelista
Ulrike Schara-Schmidt
Andreas Roos
author_sort Adela Della Marina
collection DOAJ
description Abstract Objective Immune-related adverse events (irAEs) are recognized in oncology, particularly with immune checkpoint inhibitors and other targeted therapies. Brentuximab Vedotin (BV), is an anti-CD30 antibody–drug conjugate- its association with immune-mediated myositis remains unexplored. We report a case of an adolescent with Hodgkin lymphoma (HL) who developed neuropathy and myositis following BV therapy. Materials & methods The diagnostic work-up included MRI as well as microscopic analyses (histology, electron microscopy, and immunostainings including CD30 and MxA) of a gastrocnemius muscle biopsy. Proteomic analysis was also performed on the same biopsy, and paradigmatic protein dysregulations were validated through immunostaining. Serum NCAM1 levels were measured using ELISA. Results The patient, diagnosed with HL at 15 years, developed neuropathy after Vincristine treatment and was switched to BV. During BV therapy, she experienced progressive muscle weakness and foot drop, leading to discontinuation. MRI confirmed myositis, and biopsy revealed neurogenic and inflammatory changes with complement deposition and mitochondrial dysfunction. Proteomics showed upregulation of inflammatory relevant proteins, with HPRT1 (749.43-fold) being the most increased one. Intravenous immunoglobulin (IVIG) therapy improved muscle strength. Discussion Myositis following BV therapy has not been reported. Findings suggest an immune-mediated mechanism with B-cell involvement. Given the response to IVIG, B-cell-directed therapies may be beneficial. This case identifies BV-induced myositis as a novel irAE.
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spelling doaj-art-723c5bf8fcf042df9c85c3831a14b83d2025-08-20T03:31:45ZengBMCActa Neuropathologica Communications2051-59602025-06-011311810.1186/s40478-025-02056-2Co-occurrence of myositis and neuropathy after anti-CD30 therapy in a late-adolescent Hodgkin lymphoma patientAdela Della Marina0Lydia Rink1Andreas Hentschel2Michael M. Schündeln3Christopher Nelke4Heike Kölbel5Calvin Tucht6Vera Dobelmann7Tobias Ruck8Tim Hagenacker9Teresinha Evangelista10Ulrike Schara-Schmidt11Andreas Roos12Department of Pediatric Neurology, Center for Neuromuscular Disorders in Children and Adolescents, University Hospital Essen, University of Duisburg-EssenDivision of Pediatric Hematology and Oncology, Department of Pediatrics III, University Hospital Essen, University of Duisburg-EssenLeibniz-Institut für Analytische Wissenschaften -ISAS- E.V.Division of Pediatric Hematology and Oncology, Department of Pediatrics III, University Hospital Essen, University of Duisburg-EssenDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University DüsseldorfDepartment of Pediatric Neurology, Center for Neuromuscular Disorders in Children and Adolescents, University Hospital Essen, University of Duisburg-EssenDepartment of Pediatric Neurology, Center for Neuromuscular Disorders in Children and Adolescents, University Hospital Essen, University of Duisburg-EssenDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University DüsseldorfDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University DüsseldorfDepartment of Neurology, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-EssenInstitute of Myology, Neuromuscular Morphology Unit & Neuromuscular Diseases Reference Center Nord/Est/Ile-de-France, Sorbonne Université, INSERM, GHU Pitié-SalpêtrièreDepartment of Pediatric Neurology, Center for Neuromuscular Disorders in Children and Adolescents, University Hospital Essen, University of Duisburg-EssenDepartment of Pediatric Neurology, Center for Neuromuscular Disorders in Children and Adolescents, University Hospital Essen, University of Duisburg-EssenAbstract Objective Immune-related adverse events (irAEs) are recognized in oncology, particularly with immune checkpoint inhibitors and other targeted therapies. Brentuximab Vedotin (BV), is an anti-CD30 antibody–drug conjugate- its association with immune-mediated myositis remains unexplored. We report a case of an adolescent with Hodgkin lymphoma (HL) who developed neuropathy and myositis following BV therapy. Materials & methods The diagnostic work-up included MRI as well as microscopic analyses (histology, electron microscopy, and immunostainings including CD30 and MxA) of a gastrocnemius muscle biopsy. Proteomic analysis was also performed on the same biopsy, and paradigmatic protein dysregulations were validated through immunostaining. Serum NCAM1 levels were measured using ELISA. Results The patient, diagnosed with HL at 15 years, developed neuropathy after Vincristine treatment and was switched to BV. During BV therapy, she experienced progressive muscle weakness and foot drop, leading to discontinuation. MRI confirmed myositis, and biopsy revealed neurogenic and inflammatory changes with complement deposition and mitochondrial dysfunction. Proteomics showed upregulation of inflammatory relevant proteins, with HPRT1 (749.43-fold) being the most increased one. Intravenous immunoglobulin (IVIG) therapy improved muscle strength. Discussion Myositis following BV therapy has not been reported. Findings suggest an immune-mediated mechanism with B-cell involvement. Given the response to IVIG, B-cell-directed therapies may be beneficial. This case identifies BV-induced myositis as a novel irAE.https://doi.org/10.1186/s40478-025-02056-2MyositisAnti-CD30Brentuximab vedotinChemotherapyHodgkin lymphoma
spellingShingle Adela Della Marina
Lydia Rink
Andreas Hentschel
Michael M. Schündeln
Christopher Nelke
Heike Kölbel
Calvin Tucht
Vera Dobelmann
Tobias Ruck
Tim Hagenacker
Teresinha Evangelista
Ulrike Schara-Schmidt
Andreas Roos
Co-occurrence of myositis and neuropathy after anti-CD30 therapy in a late-adolescent Hodgkin lymphoma patient
Acta Neuropathologica Communications
Myositis
Anti-CD30
Brentuximab vedotin
Chemotherapy
Hodgkin lymphoma
title Co-occurrence of myositis and neuropathy after anti-CD30 therapy in a late-adolescent Hodgkin lymphoma patient
title_full Co-occurrence of myositis and neuropathy after anti-CD30 therapy in a late-adolescent Hodgkin lymphoma patient
title_fullStr Co-occurrence of myositis and neuropathy after anti-CD30 therapy in a late-adolescent Hodgkin lymphoma patient
title_full_unstemmed Co-occurrence of myositis and neuropathy after anti-CD30 therapy in a late-adolescent Hodgkin lymphoma patient
title_short Co-occurrence of myositis and neuropathy after anti-CD30 therapy in a late-adolescent Hodgkin lymphoma patient
title_sort co occurrence of myositis and neuropathy after anti cd30 therapy in a late adolescent hodgkin lymphoma patient
topic Myositis
Anti-CD30
Brentuximab vedotin
Chemotherapy
Hodgkin lymphoma
url https://doi.org/10.1186/s40478-025-02056-2
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