American Society of Hematology Annual Meeting

Neurocognitive Outcomes Dip at 1 Month Post-CAR-T Therapy but Rebound by Month 3

Jennifer Larson
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Patient and doctor
Patient and doctor
An investigation of patients undergoing CAR-T therapy found neurocognitive outcomes decline in the first month after therapy, then patients are likely to recoup neurocognitive function by 3 months.

Patients with cancer may display worsening cognitive symptoms and declines on some performance-based measures in the month after beginning chimeric antigen receptor T-cell (CAR-T) therapy, but they may experience some improvements by the 3-month mark, according to a poster presentation at the ASH Annual Meeting 2023. 

CAR-T therapy is known for causing toxicities that can lead to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). This may raise concerns for the potential of poor cognitive outcomes in the long term, according to research from a team based in Toronto, Canada. 

With the position that more prospective data is needed to illuminate neurocognitive outcomes in patients treated with CAR-T therapy, the researchers investigated the trajectory of neurocognitive performance and self-reported cognitive functioning during the first 3 months of CAR-T therapy. 

This study was part of a larger cohort study of patients undergoing CAR-T therapy. Patients’ neurocognitive outcomes were assessed before initiating CAR-T therapy and again at months 1 and 3 after CAR-T therapy. The Functional Assessment of Cancer Therapy-Cognitive Function-Version 3 (FACT-Cog-v3) and the EORTC QLG Core Questionnaire (EORTC QLQ-C30), Cognitive Functioning scale, were used to collect self-reported assessments of cognitive functioning from the participants. 

Among the items the researchers measured with a battery of standardized neuropsychological tests were processing speed, verbal memory, and executive functioning. The raw scores were then converted to standardized z scores based on norms adjusted for age, sex, and education. 

This study used neurocognitive outcomes data from 37 patients at baseline, of whom 20 were male and 17 were female. Median age was 59 years, with a mean of 15.5 years of education. 

Outcomes data for 29 patients at 1 month were available, and 17 patients at 3 months. The frequency of overall impairment was 27% at baseline. That percentage increased to 41.4% at the 1-month mark, but dropped down to 17.6% at the 3-month mark. 

“At each time point, impairment was the most common on tests of executive function and memory,” noted researcher Samantha Mayo, PhD, RN, during a video presentation that accompanied the poster. 

Using mixed models to estimate the trajectory of neurocognitive changes over time, a statistically significant decline in mean z scores in executive function were reported at 1 month compared with baseline. However, a statistically significant improvement in executive function and memory tests were reported at 3 months, compared with baseline.

“In summary, this preliminary analysis of data from an ongoing cohort study suggests that neurocognitive impairment is present in a subgroup of patients prior to starting CAR-T therapy. 

“Patients may demonstrate declines on performance-based measures and report worsening cognitive symptoms in the first month after CAR-T therapy but also improved performance in some domains by 3 months,” Dr Mayo said. 

Future research is planned to explore differences in trajectories among different subgroups, such as patients who have experienced CRS and ICANS. 

Reference 

Mayo SJ, Edelstein K, Bernstein L, et al. Neurocognitive outcomes over the first 3 months after chimeric antigen receptor T-cell (CAR T) therapy: preliminary findings from a longitudinal study. Presented at ASH 2023. December 9-12, 2023. San Diego, CA. Abstract 3128.