Immune Checkpoint Inhibitor-Induced Hypophysitis and Patterns of Loss of Pituitary Function.
Immune Checkpoint Inhibitor-Induced Hypophysitis and Patterns of Loss of Pituitary Function.
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DOI：
10.3389/fonc.2022.836859
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发表时间：
2022
影响因子：
4.7
通讯作者：
Kluger HM
中科院分区：
文献类型：
--
作者：
Jessel S;Weiss SA;Austin M;Mahajan A;Etts K;Zhang L;Aizenbud L;Perdigoto AL;Hurwitz M;Sznol M;Herold KC;Kluger HM
免疫检查点抑制剂（ICI）在多种肿瘤类型中具有临床活性，但相关的免疫相关不良事件（irae）导致治疗延迟或停止，并对生活质量产生负面影响。垂体炎通常是一种永久性肿瘤，可影响多个垂体激素轴。在这里，我们全面描述了我们机构的临床经验与ici诱导垂体炎和相关模式的垂体功能丧失。2016年10月至2021年5月，在耶鲁癌症中心接受ICI治疗的实体肿瘤患者，主要是黑色素瘤和肾细胞癌（RCC）。从医疗记录中获得人口统计学和临床数据，包括irae的类型和时间。如果患者通过预先指定的生化和临床参数诊断为垂体炎，则纳入该队列。接受ipilimumab联合nivolumab（77%; 53/69）、anti-PD-(L)1（17%; 12/69）或ipilimumab单药治疗（6%;4/69）的黑色素瘤（n=58, 84%）、RCC （n=10,14%）和默克尔细胞癌（n= 1,1%）患者的垂体炎总发病率为69/490（14%）。在分析的69例患者中，ICI联合治疗与抗pd -1联合治疗到垂体炎的中位时间为2.8个月对4.1个月。ipilimumab联合nivolumab治疗黑色素瘤患者的垂体炎发生率为25%(46/187)，抗pd -(L)1治疗的垂体炎发生率为5%(7/129)，而RCC患者的垂体炎发生率分别为9%（7/77）和8%（3/37）。与抗pd -(L1)1单药治疗相比，联合ICI治疗并发垂体炎的患者头痛发生率（p=0.05）和并发irae发生率（p=0.01）更高。在中位2.2年的随访中，77%的患者存活。黑素瘤患者对ICI的客观反应率高于之前报道的未选择人群。中枢性甲状腺功能减退和性腺功能减退是继肾上腺轴之后最常见的垂体轴。在某些情况下，有证据表明游离睾酮水平在最初下降后会自发反弹。我们证明ICI诱导的垂体炎的发生率比以前报道的要高，这可能反映了现实世界的实践，因为随着ICI经验的增长，人们的意识也在提高。在某些情况下，有证据表明游离睾酮和/或促性腺激素反弹，但肾上腺轴激素没有反弹。
Immune checkpoint inhibitors (ICI) are clinically active across multiple tumor types but the associated immune-related adverse events (irAEs) lead to treatment delays or discontinuation and negatively impact quality-of-life. Hypophysitis is often a permanent irAE that may affect multiple pituitary hormonal axes. Here we comprehensively characterize our institution’s clinical experience with ICI-induced hypophysitis and the associated patterns of pituitary function loss. Patients with solid tumors, mostly melanoma and renal cell carcinoma (RCC), treated with ICI at Yale Cancer Center were prospectively enrolled from October 2016-May 2021. Demographics and clinical data were obtained from the medical record including type and timing of irAEs. Patients were included in this cohort if hypophysitis was diagnosed by pre-specified biochemical and clinical parameters. The overall incidence of hypophysitis was 69/490 (14%) in patients with melanoma (n=58, 84%), RCC (n=10,14%), and merkel cell carcinoma (n=1, 1%) who received ipilimumab plus nivolumab (77%; 53/69), anti-PD-(L)1 (17%; 12/69), or ipilimumab monotherapy (6%; 4/69). Of the 69 patients analyzed, median time to hypophysitis on combination ICI versus anti-PD-1 was 2.8 vs. 4.1 months. The incidence of hypophysitis in patients with melanoma was 25% (46/187) with ipilimumab plus nivolumab and 5% (7/129) with anti-PD-(L)1 compared to 9% (7/77) and 8% (3/37), respectively, in patients with RCC. Patients who developed hypophysitis on combination ICI had a higher rate of headache (p=0.05) and co-occurring irAEs (p=0.01) compared anti-PD-(L1)1 monotherapy. At a median follow-up of 2.2 years, 77% of patients were alive. Objective response rates to ICI in melanoma patients were higher than previously reported for unselected populations. Central hypothyroidism and hypogonadism were the most common pituitary axes affected after the adrenal axis. In select cases, there was evidence of spontaneous rebound in free testosterone levels after an initial decline. We demonstrate a higher rate of ICI-induced hypophysitis than previously reported, which may be reflective of real-world practice due to increased awareness as experience with ICI has grown. In select cases, there was evidence of rebound in free testosterone and/or gonadotropins but not in adrenal axis hormones.
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影响因子：
3.9
作者：
Nguyen H;Shah K;Waguespack SG;Hu MI;Habra MA;Cabanillas ME;Busaidy NL;Bassett R;Zhou S;Iyer PC;Simmons G;Kaya D;Pitteloud M;Subudhi SK;Diab A;Dadu R
通讯作者：
Dadu R
DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
2.7
作者：
Antoniou S;Bazazo G;Röckl L;Papadakis M;Berg C
通讯作者：
Berg C
影响因子：
11.5
作者：
Min, Le;Hodi, Frank Stephen;Kaiser, Ursula B.
通讯作者：
Kaiser, Ursula B.
影响因子：
158.5
作者：
Robert, Caroline;Schachter, Jacob;Ribas, Antoni
通讯作者：
Ribas, Antoni