Endocrine Abstracts

Background: Ipilimumab is a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor that improves survival in advanced melanoma. However, ipilimumab induces immune-related adverse events including hypophysitis and hypopituitarism. We describe one of the largest single centre series of ipilimumab induced hypophysitis.

Methods: We retrospectively analysed all patients (n=301) treated with ipilimumab either as a monotherapy or in combination with nivolumab for advanced melanoma at the Royal Marsden Hospital from 2010 to 2016. We reviewed clinical presentations, MRI reports and endocrine test results. Data on last contact and date of death was also collected.

Results: The overall incidence of IH was 6.9%, with an incidence of 3.3% before 2013 and 10.8% since 2013 suggesting increased awareness and recognition. There were no significant differences in age, gender or number of treatment cycles (median=3) received between the hypophysitis cohort (n=21) and no hypophysitis cohort (n=280). In the hypophysitis cohort, 17 patients reported fatigue and 18 reported headaches of which 9 had enlarged pituitary glands on MRI. Headache developed a mean of 60 days after starting treatment. Secondary adrenal insufficiency (n=21) was the most common pituitary dysfunction followed by secondary hypothyroidism (n=14) and secondary hypogonadism (n=13).

Mean TSH fell prior to cycle 3 and 4 in those who developed hypophysitis, but not in those who did not, but this did not reach significance levels, with considerable overlap of TSH levels.

The hypophysitis cohort had a significantly better overall survival compared to the no hypohysitis cohort even after accounting for patients who only received 1–2 treatment cycles.

Conclusion: IH occurred at a rate comparable to the published trials, with an increased rate in more recent years, reflecting difficulties in diagnosis. Multiple hormone deficiencies were common, requiring replacement. Patients with hypophsyitis had improved overall survival compared to those without hypophysitis, perhaps reflecting activation of the immune system.