Long-Term Nivolumab Response With Thyroid and Adrenal Side Effects

What happened, in summary

A 55-year-old man had been diagnosed one year earlier with stage IV non-small cell lung cancer. He first received pemetrexed and cisplatin through the INCYTE 266 clinical trial. Six months later, the cancer progressed in paratracheal and supraclavicular lymph nodes, so nivolumab was started every two weeks.

Routine monitoring after the sixth and seventh nivolumab doses showed a short hyperthyroid phase. Thyroid antibodies were negative, ultrasound showed no nodules, and thyroid scintigraphy showed no uptake, supporting painless thyroiditis. About four weeks later, he became hypothyroid and began levothyroxine. Nivolumab continued because his pulmonary disease remained stable.

After 33 nivolumab administrations, he developed profound fatigue, weakness, depression, poor appetite, and a 20 kg weight loss. Testing found very low cortisol and ACTH, while pituitary MRI showed no mass. Secondary adrenal insufficiency from suspected nivolumab-related hypophysitis was diagnosed. Hydrocortisone produced rapid improvement in mobility, appetite, weight, and mood.

At the last follow-up, he remained on thyroid and adrenal replacement therapy and had continued nivolumab through course 82. He was asymptomatic, had regained weight, and tumor burden had fallen to about one-fifth of baseline without progression. His experience required lifelong endocrine treatment, but the immune therapy remained effective and was never interrupted.