A Cautionary Note on Pembrolizumab use in Patients with Ascending Aortic Aneurysms.

Abstract

Case description: We describe a case of a patient treated with pembrolizumab (an immune checkpoint inhibitor) for metastatic scalp melanoma. He had a previous history of colorectal cancer, prostatic cancer and chronic polymyalgia rheumatica. The patient was known to have a stable ascending aortic aneurysm of 4.5 cm. However, he developed a rapid expansion of the ascending aortic aneurysm with the size crossing the threshold for surgery. The patient was referred to the cardiothoracic surgery service for intervention and he subsequently underwent surgery. The patient was electively admitted one week later for resection of aortic aneurysm, aortoplasty and external graft fixation. Pathologically, gross evidence of dissection was not identified; however, the histological analysis of the media showed laminar medial necrosis, multifocal in nature, with occasional clusters of histiocytic cells appreciated at their edge reminiscent of that seen in an inflammatory aortitis (granulomatous/giant cell type).

Discussion: Immune checkpoint inhibitor-induced aortitis is becoming increasingly evident, and its presentation can vary. It has been discovered incidentally on surveillance imaging with the use of nivolumab. In other cases, patients have been symptomatic to severely symptomatic. Atezolizumab with carboplatin and etoposide has been reported to cause abdominal aortitis which was responsive to corticosteroids and subsequent discontinuation of atezolizumab. Pembrolizumab has been linked to a case of transverse aortic arch aortitis. In our case, the inflammatory aortitis due to pembrolizumab was the cause of the rapid expansion of the ascending aortic aneurysm.

Conclusion: Patients with known aortic aneurysms should undergo careful surveillance when commencing immune-checkpoint inhibitor therapy.

Learning points: Immune checkpoint inhibitors are being increasingly used in the treatment of metastatic malignancy. However, they are a relatively new group of medications, and the side effect profile of each is yet to be fully recognised. Aortitis has occurred with several different immune checkpoint inhibitors.Patients with known aortic aneurysms should undergo careful surveillance when commencing immune checkpoint inhibitors.All interventional therapeutic options should be considered early in these patients on the development of aneurysmal expansion.