Journal for ImmunoTherapy of Cancer (Jul 2020)

Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: a prospective study

  • Masashi Akiyama,
  • Tomoko Kobayashi,
  • Shintaro Iwama,
  • Yoshinori Yasuda,
  • Norio Okada,
  • Takayuki Okuji,
  • Takeshi Onoue,
  • Motomitsu Goto,
  • Mariko Sugiyama,
  • Taku Tsunekawa,
  • Hiroshi Takagi,
  • Daisuke Hagiwara,
  • Hidetaka Suga,
  • Ryoichi Banno,
  • Kenji Yokota,
  • Tetsunari Hase,
  • Naozumi Hashimoto,
  • Masahiko Ando,
  • Yasushi Fujimoto,
  • Hideharu Hibi,
  • Michihiko Sone,
  • Yuichi Ando,
  • Hiroshi Arima

DOI
https://doi.org/10.1136/jitc-2020-000779
Journal volume & issue
Vol. 8, no. 2

Abstract

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Background Several immune-related adverse events (irAEs) are reported to be associated with therapeutic efficacy of immune checkpoint inhibitors, yet whether pituitary dysfunction, a life-threatening irAE, affects overall survival (OS) in patients with malignancies is unclear. This prospective study examined the association of pituitary dysfunction (pituitary-irAE) with OS of patients with non-small cell lung carcinoma (NSCLC) or malignant melanoma (MM).Methods A total of 174 patients (NSCLC, 108; MM, 66) treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab at Nagoya University Hospital were evaluated for OS and the development of pituitary-irAE. Kaplan-Meier curves of OS as a function of the development of pituitary-irAE were produced with the log-rank test as a primary endpoint.Results Pituitary-irAE was observed in 16 patients (4 (3.7%) with NSCLC, 12 (18.2%) with MM) having two different disease types: hypophysitis with deficiency of multiple anterior pituitary hormones accompanied by pituitary enlargement, and isolated adrenocorticotropic hormone (ACTH) deficiency without pituitary enlargement. Among these patients, 6 developed pituitary-irAE while being treated with ipilimumab (6/25 patients (24.0%) treated with ipilimumab) and 10 developed pituitary-irAE during treatment with nivolumab or pembrolizumab (10/167 (6.0%)). All 16 patients had ACTH deficiency and were treated with physiological doses of hydrocortisone. The development of pituitary-irAE was associated with better OS in patients with NSCLC (not reached vs 441 (95% CI not calculated) days, p<0.05) and MM (885 (95% CI 434 to 1336) vs 298 (95% CI 84 to 512) days, p<0.05).Conclusions In our study cohort, the incidence of pituitary-irAE was higher than previously reported and the development of pituitary-irAE predicted better prognosis for both NSCLC and MM when patients were treated with physiological doses of hydrocortisone.Clinical trials registration UMIN000019024.