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. 2015 Feb 15;21(4):749-55.
doi: 10.1158/1078-0432.CCR-14-2353. Epub 2014 Dec 23.

Systemic high-dose corticosteroid treatment does not improve the outcome of ipilimumab-related hypophysitis: a retrospective cohort study

Le Min  1 , Frank Stephen Hodi  2 , Anita Giobbie-Hurder  2 , Patrick A Ott  2 , Jason J Luke  3 , Hilary Donahue  2 , Meredith Davis  2 , Rona S Carroll  4 , Ursula B Kaiser  4
Affiliations

Systemic high-dose corticosteroid treatment does not improve the outcome of ipilimumab-related hypophysitis: a retrospective cohort study

Le Min et al. Clin Cancer Res. .

Abstract

Purpose: To examine the onset and outcome of ipilimumab-related hypophysitis and the response to treatment with systemic high-dose corticosteroids (HDS).

Experimental design: Twenty-five patients who developed ipilimumab-related hypophysitis were analyzed for the incidence, time to onset, time to resolution, frequency of resolution, and the effect of systemic HDS on clinical outcome. To calculate the incidence, the total number (187) of patients with metastatic melanoma treated with ipilimumab at Dana-Farber Cancer Institute (DFCI; Boston, MA) was retrieved from the DFCI oncology database. Comparisons between corticosteroid treatment groups were performed using the Fisher exact test. The distributions of overall survival were based on the method of Kaplan-Meier.

Results: The overall incidence of ipilimumab-related hypophysitis was 13%, with a higher rate in males (16.1%) than females (8.7%). The median time to onset of hypophysitis after initiation of ipilimumab treatment was 9 weeks (range, 5-36 weeks). Resolution of pituitary enlargement, secondary adrenal insufficiency, secondary hypothyroidism, male secondary hypogonadism, and hyponatremia occurred in 73%, 0%, 64%, 45%, and 92% of patients, respectively. Systemic HDS treatment did not improve the outcome of hypophysitis as measured by resolution frequency and time to resolution. One-year overall survival in the cohort of patients was 83%, and while it was slightly higher in patients who did not receive HDS, there was no statistically significant difference between treatment arms.

Conclusion: Systemic HDS therapy in patients with ipilimumab-related hypophysitis may not be indicated. Instead, supportive treatment of hypophysitis-related hormone deficiencies with the corresponding hormone replacement should be given.

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Figures

Figure 1
Figure 1. The effect of high dose corticosteroids on the frequency of resolution of each endocrinopathy
The frequency of resolution is represented as the percentage of those with resolution compared to the total number affected for each endocrinopathy. HDS: high dose corticosteroids.
Figure 2
Figure 2. The effects of high dose corticosteroids on survival rate
Kaplan-Meier estimates of overall survival with the numbers of patients at risk. The X axis was extended to 32 months (median follow-up + 18 months), the time at which there was 20% or less of the sample remaining. HDS: high dose corticosteroids.
See this image and copyright information in PMC

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