Abstract
Immune checkpoint inhibitor (ICI)-related inflammatory diseases, including polymyositis (PM) and dermatomyositis (DM), in patients suffering from neoplastic disorders represent a medical challenge. The treatment of these conditions has taken on new urgency due to the successful and broad development of cancer-directed immunological-based therapeutic strategies. While primary and secondary PM/DM phenotypes have been pathophysiologically characterized, a rational, stepwise approach to the treatment of patients with ICI-related disease is lacking. In the absence of high-quality evidence to guide clinical judgment, the available data must be critically assessed. In this literature review, we examine partially neglected immunological and clinical findings to obtain insights into the biological profiles of ICI-related PM/DM and potential treatment options. We show that differential diagnosis is essential to stratifying patients according to prognosis and therapeutic impact. Finally, we provide a comprehensive assessment of druggable targets and suggest a stepwise patient-oriented approach for the treatment of ICI-related PM/DM.
Highlights
Immune surveillance has emerged as a pivotal issue in the invasiveness of both visceral [1] and skeletal [2,3] malignancies, as it fuels a vicious cycle between the neoplastic cells and the immune microenvironment
Immune checkpoint inhibitor (ICI)-therapy-related variants are characterized by the frequent involvement of other targets of the peripheral nervous system and of the myocardium, which can be detected using specific tests: increased troponin levels suggest cardiac involvement; an electromyoneurography (EMG/ENG) study can confirm the presence of myogenic damage or the presence of neuropathic damage or neuromuscular plaque disease
Methylprednisolone; intravenous immunoglobulin (IVIG), Intravenous Immunoglobulin; PPH, Plasmapheresis; PLEX, plasma exchanges; PSL, Prednisolone; IFX, Infliximab; N/A, not available; MSA, myositis-specific autoantibodies; MAA, myositis-associated autoantibodies; SM, striated muscle; SSA/Ro52, Anti-Sjögren’s-syndrome-related antigen A/Ro52; ANA, antinuclear antibody; AChR, acetylcholine receptor; ARS, aminoacyl-tRNA synthetase; SRP, signal recognition particle; transcriptional intermediary factor 1 (TIF1)-γ, transcription intermediary factor 1-γ. * Autoantibodies were pre-existing before initiation of ICI. § RO52 is included in MAA
Summary
Immune surveillance has emerged as a pivotal issue in the invasiveness of both visceral [1] and skeletal [2,3] malignancies, as it fuels a vicious cycle between the neoplastic cells and the immune microenvironment. Among the side effects of ICI therapy is ICI-related polymyositis (PM), an inflammatory process affecting the skeletal muscles. While this condition is rare, it can be severe and potentially deadly, as it may cause rhabdomyolysis in striated muscle, including the myocardium. ICI-therapy-related variants are characterized by the frequent involvement of other targets of the peripheral nervous system and of the myocardium (myasthenia gravis [MG], polyradiculoneuritis, myocarditis), which can be detected using specific tests: increased troponin levels suggest cardiac involvement; an electromyoneurography (EMG/ENG) study can confirm the presence of myogenic damage or the presence of neuropathic damage or neuromuscular plaque disease. Any of these three compartments of myasthenia-skeletal muscle myositis or carditis can occur individually or all together, variably impacting the patient outcome
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