Case Report
Immunotherapy-induced autoimmune hypophysitis
J Oncol Pharm Practice 0(0) 1–4 ! The Author(s) 2017 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1078155217727142 journals.sagepub.com/home/opp
Gautam Valecha1, Manisha Pant1, Uroosa Ibrahim2 and Jean P Atallah2
Abstract Autoimmune hypophysitis is an immune-related adverse event of immune checkpoint inhibitors. In this article, we present the case of a 58-year-old female patient who presented to the emergency room with gradually worsening nonspecific symptoms of headache, nausea, vomiting and decreased oral intake of one week duration. The patient had been diagnosed with relapsed extensive stage small cell lung cancer. She was being treated with a combination of ipilimumab and nivolumab after progression on chemotherapy. Gadolinium-enhanced magnetic resonance imaging of head revealed pituitary enlargement up to 1.5 cm and pituitary stalk enlargement up to 4 mm consistent with hypophysitis. The patient was treated with corticosteroids resulting in rapid resolution of her symptoms. The objective of our report is to highlight this rare but important adverse event associated with checkpoint inhibitors, and discuss its clinical features, diagnostic work-up and treatment.
Keywords Immunotherapy, autoimmune hypophysitis, nivolumab, ipilimumab, adverse events Date received: 26 April 2017; revised: 25 July 2017; accepted: 29 July 2017
Introduction Immune checkpoint inhibitors represent a major breakthrough in cancer medicine. The two major classes of immune checkpoint inhibitors include monoclonal antibodies to Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and programmed death 1 receptor (PD-1) and programmed death ligand (PD-L1). The primary mechanism of action of these agents is to utilize the host’s own immune system and destroy tumor cells or inhibit tumor growth. Although this approach results in significant antitumor activity and improved survival outcomes, it is also associated with a unique spectrum of adverse events (AEs) related to autoimmune destruction. Autoimmune hypophysitis is one such rare AE associated with these novel agents. Of note, it is less commonly seen with anti-PD1/PD-L1 antibodies compared with anti-CTLA-4 antibodies.1,2 Nivolumab, an anti-PD-1 antibody and ipilimumab, an anti-CTLA-4 antibody are immunotherapeutic agents that have been evaluated in several clinical trials for the treatment of melanoma, lung cancer, prostate cancer and renal cell
carcinoma. In this report, we present a case of autoimmune hypophysitis in a patient treated with a combination of nivolumab and ipilimumab for extensive stage small cell lung cancer (SCLC).
Case A 58-year-old female presented to the emergency department with worsening headache, nausea, vomiting and decreased oral intake of one week duration. She was diagnosed with limited stage SCLC two years ago. Other medical history included hypertension, cerebral aneurysm and gastroesophageal reflux disease. Her medications included amlodipine and alprazolam. 1
Department of Medicine, Staten Island University Hospital, NY, USA Department of Hematology/Oncology, Staten Island University Hospital, NY, USA 2
Corresponding author: Gautam Valecha, Department of Medicine, Staten Island University Hospital, 475 Seaview Avenue, Staten Island, NY 10305, USA. Email: [email protected]
2 Limited stage disease was initially treated with right pneumonectomy, prophylactic whole brain irradiation and combination chemotherapy of cisplatin and etoposide. However, within a year of completing chemotherapy, her disease relapsed with metastasis to liver, adrenal glands and pancreas. A pancreatic mass biopsy suggested small cell carcinoma with positive immunohistochemical stains for CD56, TTF1 and CD45. She was then restarted on combination chemotherapy with cisplatin and etoposide that was later switched to carboplatin and etoposide. Unfortunately, her disease progressed. She was subsequently enrolled in a clinical trial and treated with combination of ipilimumab and nivolumab. After completing two cycles of nivolumab-ipilimumab combination, she developed nonspecific symptoms like nausea, vomiting, headache and decreased oral intake. A non-contrast computed tomography (CT) scan head revealed pituitary prominence which was followed by magnetic resonance imaging (MRI) that showed pituitary enlargement up to 1.5 cm and pituitary stalk enlargement up to 4 mm (see Figure 1(a) and (b)). These findings were new when compared to an MRI from six months ago. Previously noted cerebral aneurysms were stable. Biochemical testing showed adrenocorticotropic (ACTH)
Immunotherapy-induced autoimmune hypophysitis
J Oncol Pharm Practice 0(0) 1–4 ! The Author(s) 2017 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1078155217727142 journals.sagepub.com/home/opp
Gautam Valecha1, Manisha Pant1, Uroosa Ibrahim2 and Jean P Atallah2
Abstract Autoimmune hypophysitis is an immune-related adverse event of immune checkpoint inhibitors. In this article, we present the case of a 58-year-old female patient who presented to the emergency room with gradually worsening nonspecific symptoms of headache, nausea, vomiting and decreased oral intake of one week duration. The patient had been diagnosed with relapsed extensive stage small cell lung cancer. She was being treated with a combination of ipilimumab and nivolumab after progression on chemotherapy. Gadolinium-enhanced magnetic resonance imaging of head revealed pituitary enlargement up to 1.5 cm and pituitary stalk enlargement up to 4 mm consistent with hypophysitis. The patient was treated with corticosteroids resulting in rapid resolution of her symptoms. The objective of our report is to highlight this rare but important adverse event associated with checkpoint inhibitors, and discuss its clinical features, diagnostic work-up and treatment.
Keywords Immunotherapy, autoimmune hypophysitis, nivolumab, ipilimumab, adverse events Date received: 26 April 2017; revised: 25 July 2017; accepted: 29 July 2017
Introduction Immune checkpoint inhibitors represent a major breakthrough in cancer medicine. The two major classes of immune checkpoint inhibitors include monoclonal antibodies to Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and programmed death 1 receptor (PD-1) and programmed death ligand (PD-L1). The primary mechanism of action of these agents is to utilize the host’s own immune system and destroy tumor cells or inhibit tumor growth. Although this approach results in significant antitumor activity and improved survival outcomes, it is also associated with a unique spectrum of adverse events (AEs) related to autoimmune destruction. Autoimmune hypophysitis is one such rare AE associated with these novel agents. Of note, it is less commonly seen with anti-PD1/PD-L1 antibodies compared with anti-CTLA-4 antibodies.1,2 Nivolumab, an anti-PD-1 antibody and ipilimumab, an anti-CTLA-4 antibody are immunotherapeutic agents that have been evaluated in several clinical trials for the treatment of melanoma, lung cancer, prostate cancer and renal cell
carcinoma. In this report, we present a case of autoimmune hypophysitis in a patient treated with a combination of nivolumab and ipilimumab for extensive stage small cell lung cancer (SCLC).
Case A 58-year-old female presented to the emergency department with worsening headache, nausea, vomiting and decreased oral intake of one week duration. She was diagnosed with limited stage SCLC two years ago. Other medical history included hypertension, cerebral aneurysm and gastroesophageal reflux disease. Her medications included amlodipine and alprazolam. 1
Department of Medicine, Staten Island University Hospital, NY, USA Department of Hematology/Oncology, Staten Island University Hospital, NY, USA 2
Corresponding author: Gautam Valecha, Department of Medicine, Staten Island University Hospital, 475 Seaview Avenue, Staten Island, NY 10305, USA. Email: [email protected]
2 Limited stage disease was initially treated with right pneumonectomy, prophylactic whole brain irradiation and combination chemotherapy of cisplatin and etoposide. However, within a year of completing chemotherapy, her disease relapsed with metastasis to liver, adrenal glands and pancreas. A pancreatic mass biopsy suggested small cell carcinoma with positive immunohistochemical stains for CD56, TTF1 and CD45. She was then restarted on combination chemotherapy with cisplatin and etoposide that was later switched to carboplatin and etoposide. Unfortunately, her disease progressed. She was subsequently enrolled in a clinical trial and treated with combination of ipilimumab and nivolumab. After completing two cycles of nivolumab-ipilimumab combination, she developed nonspecific symptoms like nausea, vomiting, headache and decreased oral intake. A non-contrast computed tomography (CT) scan head revealed pituitary prominence which was followed by magnetic resonance imaging (MRI) that showed pituitary enlargement up to 1.5 cm and pituitary stalk enlargement up to 4 mm (see Figure 1(a) and (b)). These findings were new when compared to an MRI from six months ago. Previously noted cerebral aneurysms were stable. Biochemical testing showed adrenocorticotropic (ACTH)
