To evaluate the association between tumor gene mutation profiles, tumor mutational burden (TMB), and the occurrence of PD-1 inhibitor-induced hypophysitis.
Key Findings:
The hypophysitis group had a higher overall tumor mutational burden (6.02 vs. 5.19 mut/Mb, P = 0.002).
Significantly higher mutation rates in genes BABAM1 (18.2% vs. 0%, P = 0.014), KDM5C (18.2% vs. 0%, P = 0.014), CDH4 (19.2% vs. 1.8%, P = 0.018), and TAL1 (19.2% vs. 1.8%, P = 0.018) were found in the hypophysitis group.
PAXIP1 mutations were more common in the non-hypophysitis group (19.6% vs. 0%, P = 0.037), suggesting a potential protective role.
Interpretation:
The findings indicate a significant association between higher tumor mutational burden and specific gene mutations with the development of hypophysitis in patients treated with PD-1 inhibitors. The results suggest that certain genomic alterations may predispose patients to this adverse effect, while the presence of PAXIP1 mutations may confer a protective effect against hypophysitis. These insights could inform future research and clinical strategies aimed at predicting and managing immune-related adverse events in patients undergoing immunotherapy.
Limitations:
The study is retrospective and conducted at a single center, which may limit generalizability.
The sample size is relatively small, particularly in the hypophysitis group.
Conclusion:
The study found that patients with hypophysitis had a higher tumor mutational burden and specific mutations compared to those without hypophysitis, indicating a potential link between genomic alterations and the risk of developing this condition during PD-1 inhibitor therapy.
