Immune checkpoint inhibitor use in antisynthetase syndrome

Abstract

We report on the unique case of a patient with antisynthetase syndrome and metastatic nonsmall cell lung cancer undergoing therapy with the PD-1 checkpoint inhibitor, nivolumab. Despite adequate autoimmune disease control over a period of 12 months, the patient rapidly experienced a flare of interstitial lung disease following initial nivolumab administration, which ultimately proved fatal. The use of immune checkpoint inhibitors in patients with autoimmune disease is becoming more commonplace, however this is the first reported case of the use of these agents in a patient with antisynthetase syndrome. Additionally, the patient's initial clinical presentation with antisynthetase syndrome and simultaneous primary lung cancer, a rare association of which there are few case reports, makes this case interesting and unusual.

Efficacy and Toxicity of Immune -Checkpoint Inhibitors in Patients With Preexisting Autoimmune Disorders

“…Furthermore, for both series, the global numbers are rather small and the significance (both from statistical and clinical point of view) is debatable. Moreover, there are case reports of serious IrAE (i.e., fatal pneumonitis) that followed immune checkpoint administration in patients with pre-existing anti-synthetase syndrome (21).…”

EGFR‐mutant lung adenocarcinoma associated with antisynthetase syndrome successfully treated with osimertinib

“…Contrarily, a fatal exacerbation of ASS‐ILD following nivolumab administration has been previously reported, 14 indicating that chemotherapeutic use with ILD risks, such as immune checkpoint inhibitors, requires caution. In patients with NSCLC treated with osimertinib, the frequency of drug‐related ILD has previously been reported to be 2%–4% 16, 17 .…”

“…According to a retrospective analysis of 165 Japanese patients with ASS, 19 had cancer, of which three had lung cancer 10 . In case reports of ASS patients with NSCLC, ASS behavior was in parallel with that of tumors 13–15 . In these cases, systemic corticosteroids were first administered to stabilize ILD.…”

“…10 In case reports of ASS patients with NSCLC, ASS behavior was in parallel with that of tumors. [13][14][15] In these cases, systemic corticosteroids were first administered to stabilize ILD. NSCLC was subsequently treated, and both complete tumor resection and cytotoxic chemotherapy with or without radiotherapy were effective.…”

Case Report: The Neuromusclar Triad of Immune Checkpoint Inhibitors: A Case Report of Myositis, Myocarditis, and Myasthenia Gravis Overlap Following Toripalimab Treatment

“…A definitive link between ICIs and HMGCR antibody remains undetermined, as the reported case has a pre-existing statin induced myopathy that resolves after statin discontinuation 2 weeks prior to ICI treatment. Patients with pre-existing myositis are inclined to flares following ICI treatment (7,8). Proposed mechanisms include loss of selftolerance by disrupted balance between Treg and T effector cells, shared antigens between tumor and tissue, and epitope spreading in which release of tumor-origin and self antigens initiates inflammatory cascade (9,10).…”