Cognitive symptoms in patients with cancer receiving PD-1/PD-L1 checkpoint inhibitors: Insights from a cross-sectional pilot study.

Abstract

12094 Background: Cancer-related cognitive impairment is common with traditional therapeutic modalities, affecting memory, psychomotor speed, attention, and executive function of up to 75% of adults with cancer. Over the past decade, immune checkpoint inhibitors (ICIs) have emerged as novel and efficacious treatments due to their ability to penetrate the blood-brain barrier and improve survival rates. However, they come with significant short- and long-term complications, including neurological toxicities. Despite their benefits, the impact of ICIs on cognitive function is not well understood. This study aims to examine the frequency and severity of cognitive impairment and the factors correlated among adults with cancer receiving ICIs. Methods: We collected questionnaire data on cognitive function using the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) and other concurrent symptoms, as well as saliva samples of a subset of inflammatory cytokines from patients treated with PD-1/PD-L1 checkpoint inhibitors between 2022 and 2023. Sample characteristics were described using mean, frequency, and percentage. To analyze the relationship among symptoms and demographics, we used Pearson’s correlation and the Mann-Whitney U test. Saliva cytokines were analyzed using ELISA assays. This study is IRB approved. Results: Twenty-three patients (male: n=11, female: n=12) have received ICIs for an average of eight months, with a mean age of 70.87±11.63 years. 78.3% had melanoma/skin cancer, 8.7% had head and neck cancer, and 13% had other malignancies. Pembrolizumab was administered to 47.8%, and Nivolumab to 26.1%. The mean scores of FACT-Cog for perceived cognitive impairment (PCI) and perceived cognitive abilities (PCA) were 60.87±13.06 (maximum: 72) and 22.30±6.70 (maximum: 28), respectively. 26.1% of participants (n=6) reported lower scores than the cut-off in both PCI (cut-off: ≤55.1) and PCA (cut-off: ≤19.5). Lower FACT-Cog PCI scores were significantly correlated with older age ( r=-.511, p<.05), greater fatigue ( r=-.483, p<.05) and pain ( r=-.558, p<.01). Participants with PCA and PCI scores below the cut-off showed higher mean concentrations of IL-1β (mean±SE: 188.22±133.72 vs. 80.99±14.73pg/mL), CRP (6659.47±3027.58 vs. 3910.71±1022.41pg/mL), and IL-6 (109.24±56.07 vs. 30.22±6.26pg/mL) compared to those with scores above the cut-off, although the results were not significant. This suggests that increased inflammatory cytokines may be associated with cognitive impairment. Conclusions: This preliminary study suggests that some patients may experience cognitive impairment during ICI treatment. As cancer patients are more at risk for cognitive impairment before treatment, a longitudinal study is warranted to confirm cognitive function both pre- and post-immunotherapy, along with objective measures of cognitive performance.