Anti-synthetase syndrome associated interstitial lung disease after combination dual immune checkpoint inhibition

Abstract

Immune checkpoint inhibitors (ICIs) unleash potent anti-tumour responses but with frequent off-target immune-mediated adverse events (irAE). ICIs can induce a spectrum of rheumatologic manifestations including inflammatory arthritis, Sjögren's syndrome, scleroderma and systemic lupus erythematosus. Here, we describe a case of antisynthetase syndrome associated interstitial lung disease (ILD) following dual Programmed Cell Death 1 and Cytotoxic T Lymphocyte-Associated Protein 4 checkpoint inhibition in a patient with metastatic melanoma. Initial treatment course was complicated by a number of irAEs including pneumonitis, colitis and thyroiditis. Suspicion of an underlying systemic rheumatic disease was heightened by the severe, relapsing and fibrosing nature of the interstitial pneumonitis. A diagnosis of amyopathic antisynthetase syndrome was made upon detection of circulating aminoacyl-tRNA synthetase (anti-EJ) autoantibodies. Intensification of induction immunosuppression followed by maintenance mycophenolate, prednisone and monthly intravenous immunoglobulin achieved long-term disease control. Detection of de novo ICI-induced inflammatory myositis ILD requires a high index of suspicion and carries important prognostic and treatment implications.

Keywords: immunotherapy; interstitial lung disease; organizing pneumonia; pneumonitis.