Differences in checkpoint-inhibitor-induced hypophysitis: mono- versus combination therapy induced hypophysitis.

Autor:	van der Leij S; Department of Endocrinology, University Medical Center, Utrecht University, Utrecht, Netherlands.; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., Suijkerbuijk KPM; Department of Medical Oncology, University Medical Center, Utrecht University, Utrecht, Netherlands., van den Broek MFM; Department of Endocrinology, University Medical Center, Utrecht University, Utrecht, Netherlands.; Department of Medical Oncology, University Medical Center, Utrecht University, Utrecht, Netherlands., Valk GD; Department of Endocrinology, University Medical Center, Utrecht University, Utrecht, Netherlands.; Department of Medical Oncology, University Medical Center, Utrecht University, Utrecht, Netherlands., Dankbaar JW; Department of Radiology, University Medical Center, Utrecht University, Utrecht, Netherlands., van Santen HM; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.; Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, University Medical Center, Utrecht University, Utrecht, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2024 Jul 29; Vol. 15, pp. 1400841. Date of Electronic Publication: 2024 Jul 29 (Print Publication: 2024).
DOI:	10.3389/fendo.2024.1400841
Abstrakt:	Objective: Immune checkpoint inhibitors (ICIs) are revolutionary in oncology but may cause immune-related (IR) side effects, such as hypophysitis. Treatment with anti-PD-(L)1, anti-CTLA-4 or anti-CLTA-4/PD-1 may induce hypophysitis, but little is known about the differences in clinical presentation or need for different treatment. We analyzed the differences of anti-PD-(L)1, anti-CTLA-4 and anti-CTLA-4/PD-1 induced hypophysitis. Methods: retrospective analysis of 67 patients (27 anti-PD-(L)1, 6 anti-CLTA-4 and 34 anti-CTLA-4/PD-1 induced hypophysitis). Results: The median time between starting ICIs and IR-hypophysitis was longer after anti-PD(L)-1) therapy (22 weeks versus 11 and 14 weeks after anti-CTLA-4 and anti-CTLA-4/PD-1 therapy, respectively). The majority of patients (>90%), presented with atypical complaints such as fatigue, nausea, and muscle complaints. Headache, TSH or LH/FSH deficiency were more common in anti-CTLA-4 and anti-CLTA-4/PD-1 versus anti-PD-(L)1 induced hypophysitis (83% and 58% versus 8%, 67% and 41% versus 11%, and 83% and 48% versus 7%, respectively). Pituitary abnormalities on MRI (hypophysitis or secondary empty sella syndrome) were only seen in patients receiving anti-CTLA-4 or anti-CTLA-4/PD-1 therapy. Recovery from TSH, LH/FSH and ACTH deficiency was described in 92%, 70% and 0% of patients after a mean period of 14 and 104 days, respectively, and did not differ between patients who did or did not receive high-dose steroids. Conclusion: The clinical presentation of IR-hypophysitis varies depending on the type of ICIs. MRI abnormalities were only seen in anti-CTLA-4 or anti-CTLA-4/PD-1 induced hypophysitis. Endocrine recovery is seen for LH/FSH and TSH deficiency but not for ACTH deficiency, irrespective of the corticosteroid dose. Competing Interests: KS has consulting/advisory relationships with Bristol-Myers Squibb, Merck Sharp and Dome, Abbvie, Pierre Fabre Novartis, Sairopa, received honoraria from Novartis, Roche, Merck Sharp and Dome and received research funding from TigaTx, Bristol Myers Squibb and Philips. HS has received research funding from Pfizer Quality Improvement Grant and travel plus accommodation costs for an international meeting from Rhythm Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 van der Leij, Suijkerbuijk, van den Broek, Valk, Dankbaar and van Santen.)
Databáze:	MEDLINE
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