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

TL;DR

A late-adolescent Hodgkin lymphoma patient developed myositis and neuropathy after treatment with Brentuximab Vedotin, suggesting a new immune-related side effect.

Contribution

This is the first reported case of myositis associated with Brentuximab Vedotin therapy, highlighting a novel immune-related adverse event.

Findings

MRI and biopsy confirmed myositis with neurogenic and inflammatory changes.

Proteomic analysis revealed significant upregulation of inflammatory proteins, including HPRT1.

The patient showed improvement with intravenous immunoglobulin therapy.

Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1186/s40478-025-02056-2.

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