Literature DB >> 31176301

Hypophysitis secondary to nivolumab and pembrolizumab is a clinical entity distinct from ipilimumab-associated hypophysitis.

Alexander Faje1, Kerry Reynolds2, Leyre Zubiri2, Donald Lawrence3, Justine V Cohen3, Ryan J Sullivan3, Lisa Nachtigall1, Nicholas Tritos1.   

Abstract

OBJECTIVE: Little has been published describing hypophysitis after nivolumab or pembrolizumab treatment. We aimed to (i) assess the risk of hypophysitis following nivolumab or pembrolizumab treatment, (ii) characterize the clinical presentation and outcomes in these patients and (iii) compare these patients to hypophysitis following ipilimumab and ipilimumab plus nivolumab (combo). We hypothesized that headaches, pituitary enlargement on MRI and multiple anterior pituitary hormone deficiencies would occur less often in the nivolumab/pembrolizumab group versus ipilimumab or combo hypophysitis patients. DESIGN AND METHODS: We conducted a multi-center retrospective review utilizing the Research Patient Database registry to evaluate individuals diagnosed with hypophysitis following treatment with nivolumab/pembrolizumab (n = 22), ipilimumab (n = 64) and combo (n = 20). Encounter notes, radiologic imaging and laboratory results for these patients were comprehensively reviewed.
RESULTS: Hypophysitis was rare following treatment with nivolumab/pembrolizumab (0.5%, 17/3522) compared to ipilimumab (13.6%, 34/250), P < 0.0001. Hypophysitis was diagnosed later in nivolumab/pembrolizumab (median: 25.8 weeks, interquartile range (IR): 18.4-44.0) compared to ipilimumab (9.3, IR: 7.2-11.1) or combo patients (12.5, IR: 7.4-18.6), P < 0.0001 for both. Headache and pituitary enlargement occurred less commonly in nivolumab/pemrolizumab patients (23% and 5/18, respectively) compared to ipilimumab (75%, 60/61) and combo (75%, 16/17) treatment groups (P < 0.0001 versus ipilimumab and P = 0.001 versus combo for headache and P < 0.0001 for both for enlargement).
CONCLUSIONS: This study represents the first comprehensive cohort analysis of nivolumab or pembrolizumab-associated hypophysitis in a large patient group. Hypophysitis occurs rarely with these medications, and these patients have a distinct phenotype compared to hypophysitis after treatment with ipilimumab or ipilimumab plus nivolumab.

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Year:  2019        PMID: 31176301     DOI: 10.1530/EJE-19-0238

Source DB:  PubMed          Journal:  Eur J Endocrinol        ISSN: 0804-4643            Impact factor:   6.664


  35 in total

1.  Endocrine Autoantibodies Determine Immune Checkpoint Inhibitor-induced Endocrinopathy: A Prospective Study.

Authors:  Artak Labadzhyan; Kristopher Wentzel; Omid Hamid; Kamlynn Chow; Sungjin Kim; Lawrence Piro; Shlomo Melmed
Journal:  J Clin Endocrinol Metab       Date:  2022-06-16       Impact factor: 6.134

Review 2.  Hypophysitis: An update on the novel forms, diagnosis and management of disorders of pituitary inflammation.

Authors:  Sriram Gubbi; Fady Hannah-Shmouni; Joseph G Verbalis; Christian A Koch
Journal:  Best Pract Res Clin Endocrinol Metab       Date:  2019-12-12       Impact factor: 4.690

Review 3.  Endocrine toxicities of immune checkpoint inhibitors.

Authors:  Jordan J Wright; Alvin C Powers; Douglas B Johnson
Journal:  Nat Rev Endocrinol       Date:  2021-04-19       Impact factor: 43.330

4.  Hyponatremia and other electrolyte abnormalities in patients receiving immune checkpoint inhibitors.

Authors:  Harish Seethapathy; Nifasha Rusibamayila; Donald F Chute; Meghan Lee; Ian Strohbehn; Leyre Zubiri; Alexander T Faje; Kerry L Reynolds; Kenar D Jhaveri; Meghan E Sise
Journal:  Nephrol Dial Transplant       Date:  2021-12-02       Impact factor: 5.992

5.  Anti-pituitary antibodies and susceptible human leukocyte antigen alleles as predictive biomarkers for pituitary dysfunction induced by immune checkpoint inhibitors.

Authors:  Tomoko Kobayashi; Shintaro Iwama; Daisuke Sugiyama; Yoshinori Yasuda; Takayuki Okuji; Masaaki Ito; Sachiko Ito; Mariko Sugiyama; Takeshi Onoue; Hiroshi Takagi; Daisuke Hagiwara; Yoshihiro Ito; Hidetaka Suga; Ryoichi Banno; Hiroyoshi Nishikawa; Hiroshi Arima
Journal:  J Immunother Cancer       Date:  2021-05       Impact factor: 13.751

Review 6.  Hypophysitis induced by immune checkpoint inhibitors: a 10-year assessment.

Authors:  Giulia Di Dalmazi; Silvia Ippolito; Isabella Lupi; Patrizio Caturegli
Journal:  Expert Rev Endocrinol Metab       Date:  2019-11

7.  Pembrolizumab in the adjuvant treatment of melanoma: efficacy and safety.

Authors:  Caroline A Nebhan; Douglas B Johnson
Journal:  Expert Rev Anticancer Ther       Date:  2021-02-14       Impact factor: 3.627

8.  The Diagnosis and Management of Endocrine Side Effects of Immune Checkpoint Inhibitors.

Authors:  Knut Mai; Martin Fassnacht; Dagmar Führer-Sakel; Jürgen B Honegger; Matthias M Weber; Matthias Kroiss
Journal:  Dtsch Arztebl Int       Date:  2021-06-11       Impact factor: 5.594

9.  Immune checkpoint inhibitor combination therapies very frequently induce secondary adrenal insufficiency.

Authors:  Katsunori Manaka; Junichiro Sato; Maki Takeuchi; Kousuke Watanabe; Hidenori Kage; Taketo Kawai; Yusuke Sato; Takuya Miyagawa; Daisuke Yamada; Haruki Kume; Shinichi Sato; Takahide Nagase; Taroh Iiri; Masaomi Nangaku; Noriko Makita
Journal:  Sci Rep       Date:  2021-06-02       Impact factor: 4.379

Review 10.  Immune-related toxicities of checkpoint inhibitors: mechanisms and mitigation strategies.

Authors:  Ryan J Sullivan; Jeffrey S Weber
Journal:  Nat Rev Drug Discov       Date:  2021-07-27       Impact factor: 112.288

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