To describe a novel neuromuscular complication of mogamulizumab, a monoclonal antibody used in the treatment of cutaneous T-cell lymphoma (CTCL).

Neuromuscular immune-related adverse events (irAEs) are well described in association with immune-checkpoint inhibitor therapy, including myositis, myasthenia gravis, and myocarditis overlap syndromes. IrAEs are also seen with the novel CTCL therapy mogamulizumab, which works by binding chemokine receptor 4 (CCR4), enhancing antibody-dependent cellular cytotoxicity of both lymphoma cells and regulatory T cells (Tregs). Treg depletion results in loss of suppression of cytotoxic T cells, thereby causing irAEs. Most mogamulizumab-associated irAEs are dermatologic, however rare cases of myositis, myasthenia gravis, and/or myocarditis have been reported. Although rare, the incidence of neuromuscular irAEs in a series of patients treated with mogamulizimab was 5/42, or 11.9%[1].

A 73-year-old man with a history of previously treated Sézary syndrome developed dysphagia, dysarthria, exertional dyspnea, limb weakness, and diffuse myalgias seven weeks after starting mogamulizumab.  Exam showed mild weakness of eye closure and cheek puff, hypophonia, and mild neck flexion and proximal arm and leg weakness, with preserved sensation and deep tendon reflexes.  CK was elevated to 2669, and EMG showed evidence of a myopathic process with muscle membrane irritability.  AChR binding and MuSK antibody testing was negative.  Mogamulizumab was discontinued.  Treatment with high dose IV steroids followed by oral steroid taper led to modest improvement in symptoms and decrease in CK; monthly IVIG was added but dysphagia and CKs in the 600-900 range persisted.

Neuromuscular irAEs may be seen in association with mogamulizumab therapy due to Treg depletion and the associated dysregulation of cytotoxic T-cell activity.