Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma.

Abstract

OBJECTIVE:

Few data are published on the long-term follow-up of ipilimumab-induced hypophysitis, a cytotoxic T-lymphocyte antigen 4 antibody. We characterized hypophysitis in terms of clinical signs, endocrinological profile, and imaging at diagnosis and during a long-term follow-up.

DESIGN AND PATIENTS:

Fifteen patients, treated for malignant melanoma and who presented ipilimumab-induced hypophysitis, were observed between June 2006 and August 2012 in Timone Hospital, Marseille.

METHODS:

Symptoms, pituitary function, and pituitary imaging at diagnosis of hypophysitis and during the follow-up were recorded.

RESULTS:

Of 131 patients treated with ipilimumab or a placebo, 15 patients (10 mg/kg in 11/15) presented with hypophysitis (≥11.5%) at 9.5±5.9 weeks (mean±s.d.) after treatment start, occurring in 66% after the third infusion. The main initial symptoms were headache (n=13) and asthenia (n=11). All patients but one had at least one hormonal defect: thyrotroph (n=13), gonadotroph (n=12), or corticotroph (n=11) deficiencies. None had diabetes insipidus. Pituitary imaging showed a moderately enlarged gland in 12 patients. Clinical symptoms improved rapidly on high-dose glucocorticoids (n=11) or physiological replacement doses (n=4). At the end of follow-up (median 33.6 months, range 7-53.5), corticotroph deficiency remained in 13 patients, 11 recovered thyrotroph and ten gonadotroph functions. Pituitary imaging remained abnormal in 11 patients.

CONCLUSION:

Ipilimumab-induced hypophysitis is a common side-effect with frequent hormonal deficiencies at diagnosis. Usually, hormonal deficiencies improved, except for corticotroph function. Patients receiving these immunomodulatory therapies should be closely monitored especially by systematic baseline hormone measurements after the third infusion and remain at a risk of adrenal insufficiency in the long-term.

• Authors: Frédérique Albarel, Caroline Gaudy, Frédéric Castinetti, Tiphaine Carré, Isabelle Morange, Bernard Conte-Devolx, Jean-Jacques Grob, Thierry Brue
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 172 Issue 2 Pg. 195-204 (Feb 2015) ISSN: 1479-683X [Electronic] England
• PMID: 25416723 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 European Society of Endocrinology.

Chemical References

• Antibodies, Monoclonal
• CTLA-4 Antigen
• Ipilimumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal (adverse effects)
• CTLA-4 Antigen (blood)
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Ipilimumab
• Male
• Melanoma (blood, drug therapy)
• Middle Aged
• Pituitary Diseases (blood, chemically induced, diagnosis)
• Skin Neoplasms (blood, drug therapy)
• Time Factors