Combination immunotherapy of nivolumab plus ipilimumab in a lung cancer patient with Werner syndrome; a case report

Werner syndrome (WS) is a rare progressive disorder that is characterized by premature aging of all organs. Malignancy is a frequent complication of WS, however, lung cancer patients with WS are much rare. In patients with WS, the treatment for malignancy is often limited due to other complications of severe skin ulcer, diabetes mellitus and cardiovascular disease. Currently, immune-checkpoint inhibitors (ICIs) are standard therapy for several cancer patients and the combination of nivolumab plus ipilimumab has also been approved for the treatment of non-small cell lung cancer (NSCLC). Recent studies have also reported that serious immune-related adverse events (irAEs) induced by ICIs may correlate with elderly or more vulnerable patients. However, the efficacy and safety of ICIs in NSCLC patients with WS remain unclear. To the best of our knowledge, this is the first case describing a NSCLC patient with WS receiving the combination immunotherapy of nivolumab and ipilimumab. Our case showed objective response to ICIs, however, several immune-related adverse events (irAEs) including hypothyroidism, adrenal insufficiency, hard rash and interstitial lung disease occurred, thus resulted in early treatment discontinuation. Our case suggests that immunotherapy for NSCLC patients with WS could be effective, but physicians may be aware of the possibility of multiple irAEs undergoing immunotherapy for NSCLC patients with WS.