1070P Patterns of adverse reactions for immune checkpoint inhibitors in cancer patients with central nervous system metastases

T. Gu,H. Yang, J. Shen, A. Lin,J. Zhang, P. Luo

Annals of Oncology(2023)

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Abstract
Immune checkpoint inhibitors (ICIs) have yielded promising results in the treatment of cancer patients with central nervous system (CNS) metastases. However, due to a dearth of clinical research, it is necessary to further elucidate the side effects of ICIs in patients with CNS metastases. We identified patients with CNS metastases treated with ICIs from Q1 2013 to Q2 2022 by scrutinizing the FDA Adverse Event Reporting System (FAERS) database. Following removal of duplicate data, the study collected 511 cases. Subsequently, disproportionality analysis was performed. Risk factors were explored using univariate and multivariate logistic regression. Moreover, the influence of clinical factors on the time to onset of adverse reactions was examined. The study revealed a higher susceptibility to psychiatric complications, including confusion state, insomnia, mania, and memory impairment, following ICIs treatment in CNS metastasis patients. Furthermore, rare but severe retinal detachment may arise due to anti-PDL1 drug usage, whereas co-administration of anti-PD1 and anti-CTLA4 drugs may produce nephrotoxicity concerns. Multivariate logistic regression analysis demonstrated that the combined therapy of anti-PD1+anti-CTLA4 therapy was an independent risk factor for adverse nephrotoxic reactions in CNS metastasis patients (OR: 2.75, 95%CI: 1.37-5.46, P<0.05). The onset time of complications differed depending on the immunotherapeutic strategy. Anti-PD-L1 therapy had a later onset time of complications (Median: 67 days, IQR: 28.75-114.25) compared to that of anti-PD1 (Median: 33 days, IQR: 10-90) and anti-CTLA4 therapy (Median: 29 days, IQR:10.5-52.5), respectively. Furthermore, our study indicated that younger patients exhibited a higher probability of fatal complications (OR: 0.97, 95%CI: 0.95-0.99, P=0.02) and experienced a shorter time to onset of complications (r=2.27, P=0.007). This study employed a massive database to investigate the spectrum of adverse reactions resulting from ICIs therapy administered to CNS metastasis patients, thereby providing vigilance data for broader clinical applications.
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Key words
immune checkpoint inhibitors,central nervous system metastases,cancer patients
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