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October 5, 2025

P06.01.a the Cognitive Sequelae of Immunotherapy: Initial Results From a Longitudinal Prospective Study in Patients With Solid Malignancies

Key Points

Cognitive function showed minor deterioration in attention, motor skill, and executive function at 12 months, but recovery was observed by 18 months.
Among 11 patients tested, attention scores dropped from 97.2 to 91.3 normalized units at the 12-month mark.
The study utilized a computerized battery (Neurotrax©) to assess cognitive domains over multiple time points.
Continued research is essential to fully understand the clinical implications of these cognitive changes, particularly due to the small sample size.

Abstract

Abstract BACKGROUND Data regarding the cognitive sequelae of immunotherapy is limited. This study aims to evaluate changes in cognitive performance among patients treated with immunotherapy for any solid malignancy. METHODS Patients aged 18-75 receiving immunotherapy in the adjuvant or metastatic setting were evaluated using a computerized testing battery (Neurotrax©) at 4 separate time points: baseline prior to commencing treatment (T0), six months (T1), 12 months (T2) and 18 months (T3). Seven cognitive domains were assessed, including memory and attention. A Global Cognitive Score (GCS) was provided at each timepoint. Depression and anxiety were evaluated using questionnaires, alongside B12 and TSH levels, in order to exclude alternative causes for cognitive decline. Patients with brain metastases were excluded. RESULTS 21 patients were recruited between July 2021 - December 2024. Among 11 patients who completed ≥3 testing sessions thus far, deteriorations were recorded at T2 compared to baseline in the mean scores for attention (97.2 vs 91.3 normalized units), motor skill (104.5 vs 100 normalized units) and executive function (100.7 vs 97.8 normalized units). Notably, mean Global Cognitive Scores remained stable. All domains returned to baseline performance at T3, except for motor skills which showed improvement but failed to reach pre-treatment baseline scores. There was no association between diagnosis or treatment protocol and observed cognitive changes. CONCLUSION Cognitive function under immunotherapy demonstrated minor deteriorations in three domains (motor skill, executive function and attention) at 12 months post-treatment initiation, with near complete recovery at 18 months. Global Cognitive Scores (GCS) remained stable. The clinical correlates of the observed minute changes is unclear. Furthermore, the small sample size prohibits the generalization of our findings to the broad treatment population and will require further research. The study is currently ongoing and we hope to update the results after completion of patient recruitment and follow-up.

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