Min Le, Hodi Frank Stephen, Giobbie-Hurder Anita, Ott Patrick A, Luke Jason J, Donahue Hilary, Davis Meredith, Carroll Rona S, Kaiser Ursula B
Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Clin Cancer Res. 2015 Feb 15;21(4):749-55. doi: 10.1158/1078-0432.CCR-14-2353. Epub 2014 Dec 23.
To examine the onset and outcome of ipilimumab-related hypophysitis and the response to treatment with systemic high-dose corticosteroids (HDS).
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.
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.
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.
研究伊匹单抗相关垂体炎的发病情况、结局以及全身大剂量皮质类固醇（HDS）治疗的反应。
对25例发生伊匹单抗相关垂体炎的患者进行分析，以确定其发病率、发病时间、缓解时间、缓解频率以及全身HDS对临床结局的影响。为计算发病率，从达纳-法伯癌症研究所（DFCI；马萨诸塞州波士顿）的肿瘤数据库中检索接受伊匹单抗治疗的转移性黑色素瘤患者总数（187例）。使用Fisher精确检验对皮质类固醇治疗组进行比较。总生存分布基于Kaplan-Meier方法。
伊匹单抗相关垂体炎的总体发病率为13%，男性发病率（16.1%）高于女性（8.7%）。开始伊匹单抗治疗后垂体炎发病的中位时间为9周（范围5 - 36周）。垂体肿大、继发性肾上腺功能不全、继发性甲状腺功能减退、男性继发性性腺功能减退和低钠血症的缓解率分别为73%、0%、64%、45%和92%。全身HDS治疗并未改善垂体炎的结局，以缓解频率和缓解时间衡量均如此。该队列患者的一年总生存率为83%，未接受HDS治疗的患者总生存率略高，但治疗组之间无统计学显著差异。
伊匹单抗相关垂体炎患者可能无需进行全身HDS治疗。相反，应给予相应激素替代疗法对垂体炎相关激素缺乏进行支持治疗。
