POS0576 ANTI-TIF1-Γ POSITIVE DERMATOMYOSITIS WITH SEVERE OROPHARYNGEAL INVOLVEMENT AFTER IMMUNE CHECKPOINT INHIBITORS

Abstract

BackgroundAnti-TIF1-γ antibody is specifically associated with paraneoplastic dermatomyositis (DM)[1], but this serum marker has seldom been reported after cancer immunotherapy. Immune checkpoint inhibitors frequently cause immune-mediated endocrine, gastrointestinal, and cutaneous syndromes[2]and de novo DM cases have also been described and successfully treated using glucocorticoids and intravenous immunoglobulin (IVIG)[3].ObjectivesWe report the case of a man developing anti-TIF1-γ positive DM following immunotherapy with progressively worsening dysphagia refractory to glucocorticoids, immunosuppressants, and IVIG.MethodsCase report.ResultsIn February 2021 a 47-year-old man was diagnosed with skin melanoma that was surgically resected and treated with adjuvant ipilimumab and nivolumab, leading to complete remission. After three months, he developedde novothyroiditis, hepatitis, colitis, and experienced rapid progression of previous vitiligo, along with muscle weakness and 5X CK elevation. His rheumatological workup included positive ANA at indirect immunofluorescence (1:640 titer, speckled pattern), and high-titer anti-TIF1-γ antibodies. Inflammatory myositis was diagnosed and treated with glucocorticoids (prednisone 1 mg/kg) and mofetil mycophenolate (MMF, 3 g/d) with initial benefit on muscle function. In September 2021, the patient had a metastasis-negative lymph node evaluation and suspended MMF for surgery with a subsequent rapidly progressive deterioration of muscle function, with dysphonia, dysphagia, and typical DM skin lesions (Figure 1) with pancytopenia (hemoglobin 9 g/dL, white blood cells 1500/mmc, platelets 40.000/mmc). Further oncological evaluation (total body CT scan, brain MRI) was negative for the recurrence of malignancy or the presence of myasthenia gravis and neuropathy. Methylprednisolone pulses (500 mg for 3 days) were started, followed by high dose IVIG (5 g/kg), with marginal improvement on muscle function, normalization of CK levels, but no effect on dysphagia which required PEG tube placement. MMF was restarted but rapidly stopped because of septic shock requiring intensive care unit admission, followed by recurrent severe infections, contraindicating further immunosuppression. Six monthly high-dose IVIG infusions were continued[4]with minimal effect. Worsening tetra-paresis, absolute dysphagia, impaired cough, and inability to manage salivary secretions led to massive aspiration pneumonia. The man developed acute respiratory insufficiency, septic shock, and multiorgan failure, and died 13 months after the onset of DM.ConclusionWorsening myopathy, typical skin lesions, and concomitant immune-related adverse events should raise suspicion of DM in patients receiving immune checkpoint inhibitors[3]. Balancing the risks of DM disease flare, malignancy, and severe infections is of paramount importance when choosing the most appropriate therapy. Patients with anti-TIF1-γ DM following immunotherapy may also manifest tetra-paresis, dysphagia, and severe pancytopenia.