Immune Checkpoint Inhibitor Therapy for Aggressive Pituitary Neuroendocrine Tumors Journal Article
| Authors: | Lin, A. L.; Rudneva, V.; Newton, A.; Majd, N. K.; Magge, R.; Sengupta, S.; Goichot, B.; Piotrowski, A.; Gavrilovic, I.; Cooper, O.; Rosenblum, M.; Kaley, T.; Mellinghoff, I.; Young, R. J.; Donoghue, M. T. A.; Tabar, V.; Geer, E. B. |
| Article Title: | Immune Checkpoint Inhibitor Therapy for Aggressive Pituitary Neuroendocrine Tumors |
| Abstract: | Context Pituitary neuroendocrine tumors (PitNETs) that progress following surgery and radiotherapy are in need of additional treatment options. Responses to immune checkpoint inhibitors (ICIs) have been described; however, the feasibility of ICI therapy and biomarkers of response have not been formally assessed.Objective To evaluate the activity of ICI as a treatment for PitNETs.Methods We performed a single-center, prospective, phase 2 trial investigating the activity of ipilimumab and nivolumab in patients with PitNETs. The primary endpoint was objective response using the iRANO response criteria. We then explored genetic biomarkers of response to ICIs in 13 patients with PitNETs who were treated with ICIs, on or outside of the trial.Results Ten patients with a PitNET were enrolled, including 5 corticotroph, 4 lactotroph, and 1 somatotroph tumor, of which 9/10 (4 metastatic and 5 nonmetastatic) patients were evaluable for the primary endpoint. While no objective responses were observed, tumor shrinkage was seen in 2/9 patients. In a biomarker discovery cohort, comprising 7 tumors treated on trial and 6 tumors treated off trial, temozolomide hypermutation, and mismatch repair deficiency (MMRd) were associated with immunological response. In 3 tumors sequenced pre- and post-ICI treatment, we identified evidence of immunoediting, characterized by loss of MMRd and/or a decrease in tumor mutational burden.Conclusion This study demonstrates the safety and feasibility of ICI treatment in aggressive PitNETs. We also identified MMRd and temozolomide hypermutation as potential biomarkers of response to ICI. Overall, our data suggest that ICIs might provide an additional treatment option for PitNET; this should be evaluated more broadly in future studies. |
| Keywords: | biomarkers; immunotherapy; clinical trials; patient; european-society; mutational processes; pituitary neuroendocrine tumors |
| Journal Title: | Journal of Clinical Endocrinology and Metabolism |
| ISSN: | 0021-972X |
| Publisher: | Oxford University Press |
| Publication status: | Online ahead of print |
| Date Published: | 2025-01-01 |
| Online Publication Date: | 2025-01-01 |
| Language: | English |
| ACCESSION: | WOS:001462130100001 |
| DOI: | 10.1210/clinem/dgaf178 |
| PROVIDER: | wos |
| Notes: | Article; Early Access -- Source: Wos |
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