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Immune-mediated necrotizing myositis in patients receiving immune checkpoint inhibitors: clinical and histopathological features, treatment and outcome (N6.002)

2018; Lippincott Williams & Wilkins; Volume: 90; Issue: 15_supplement Linguagem: Inglês

10.1212/wnl.90.15_supplement.n6.002

1526-632X

Mehdi Touat, Thierry Maisonobe, Samuel Knauß, Omar Ben-Hadj Salem, B. Hervier, Karine Auré, Tali‐Anne Szwebel, N. Kramkimel, Claire Lethrosne, Jean-Frédéric Bruch, Pauline Laly, J. Cadranel, Anthony Béhin, Yves Allenbach, Olivier Benveniste, Timothée Lenglet, Dimitri Psimaras, Werner Stenzel, Sarah Léonard-Louis,

Cancer Immunotherapy and Biomarkers

Objective: To assess the clinical, histopathologic features and outcome of myositis triggered by immune checkpoint inhibitors (ICIs). Background: Myositis has been recently recognized as an emerging complication of ICIs; however, the clinical and histopathological features of this rare complication are unclear. Design/Methods: We analyzed patients consecutively diagnosed with ICI-related myositis in tertiary centers in Paris and Berlin, from 2015 to 2017. Diagnosis was based on presence of ≥ 3/4 of: objective muscle weakness, elevated serum creatine kinase (CK) levels, electromyoneurography (EMNG) showing myopathic process without decrement during repetitive nerve stimulation (RNS), and/or myositis on muscle biopsy. Main outcomes were clinical and histopathological findings, including MHC-I, C5b-9, CD3, CD4, CD8, CD20, CD68, PD-1, PD-L1 and PD-L2 immunohistochemistry. EMNG, CK levels and autoantibodies were assessed. Results: Ten patients with metastatic cancer were included; median age was 73 years (range, 56–87). Six patients developed myositis during nivolumab therapy, one during pembrolizumab, one during durvalumab, and two during combined nivolumab and ipilimumab. Median delay between ICI initiation and myositis onset was 25 days (range, 5–87). Clinical manifestations were dominated by acute/subacute myalgias (8 patients), limb-girdle (7), axial (7) and oculomotor (7) weakness. Four patients had evidence of myocarditis. In all patients, CK levels were markedly elevated (median 2668 U/L, range 1059–16620), while anti-acetylcholine receptor and myositis-associated autoantibodies were negative. EMNG showed myopathic process without decrement during RNS in all patients. Muscle biopsy constantly showed multifocal necrotic muscle fibers, MHC-I overexpression and endomysial inflammatory infiltrates, mainly consisting of CD68+ and CD8+ cells. ICI treatment was withdrawn in all patients; nine received immunosuppressants, which resulted in marked clinical improvement. Conclusions: The clinical phenotype of ICI-related myositis is remarkably homogeneous, consisting of an unusual axial phenotype including eye-movement disorders. Morphological characteristics are unique and expand the nosological spectrum of inflammatory myopathies. ICI withdrawal and treatment with immunosuppressants are associated with clinical improvement. Disclosure: Dr. Touat has nothing to disclose. Dr. Maisonobe has nothing to disclose. Dr. Knauss has nothing to disclose. Dr. Ben-Hadj Salem has nothing to disclose. Dr. Hervier has nothing to disclose. Dr. Aure has nothing to disclose. Dr. Szwebel has nothing to disclose. Dr. Kramkimel has nothing to disclose. Dr. Lethrosne has nothing to disclose. Dr. Bruch has nothing to disclose. Dr. Laly has nothing to disclose. Dr. Cadranel has nothing to disclose. Dr. Behin has nothing to disclose. Dr. Allenbach has nothing to disclose. Dr. Benveniste has nothing to disclose. Dr. Lenglet has nothing to disclose. Dr. Psimaras has nothing to disclose. Dr. Stenzel has nothing to disclose. Dr. Leonard-Louis has nothing to disclose.