Nivolumab rechallenge after pituitary apoplexy associated with nivolumab plus ipilimumab in a patient with pituitary adenoma and rectal melanoma: a case report and literature review

The overall incidence of pituitary apoplexy among patients with pituitary adenoma ranges from 0.6% to 7.0%, although many cases likely go undiagnosed. Several precipitating factors have been identified, and a small number of case reports have suggested an association between immune checkpoint inhibitors and pituitary apoplexy, particularly in patients with preexisting adenoma. Moreover, the safety of immune checkpoint inhibitor rechallenge remains uncertain. The patient was a 71-year-old woman with a recurrence of metastatic primary rectal melanoma. A pituitary tumor had been identified before initiation of systemic therapy. Following the second cycle of nivolumab plus ipilimumab, the patient developed headache, nausea, and vomiting, followed by decreased serum thyroid-stimulating hormone, adrenocorticotrophic hormone, and luteinizing hormone levels. These findings were consistent with evolving hypopituitarism. Contrast-enhanced magnetic resonance images revealed hemorrhage in the pituitary adenoma, suggesting pituitary apoplexy. Eight months after discontinuation of nivolumab plus ipilimumab, disease progression was noted, and nivolumab monotherapy was resumed. There was no recurrence of pituitary apoplexy during six cycles of nivolumab. This case highlights that pituitary apoplexy can occur temporally after nivolumab plus ipilimumab treatment in patients with preexisting pituitary adenoma. Importantly, nivolumab monotherapy rechallenge under close monitoring may be feasible without recurrence of pituitary apoplexy.