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. 2025 Apr;31(4):236.e1-236.e13.
doi: 10.1016/j.jtct.2025.01.886. Epub 2025 Jan 25.

Long-Term Cognitive Outcomes in Adult Patients Receiving Chimeric Antigen Receptor T-Cell Therapies

Anna Barata  1 , P Connor Johnson  2 , Tejaswini M Dhawale  2 , Richard A Newcomb  2 , Hermion L Amonoo  3 , Mitchell W Lavoie  4 , Dagny Vaughn  5 , Kyle Karpinski  6 , Bridget Coffey  6 , Giuliana V Zarrella  7 , Melissa M Gardner  6 , Jorg Dietrich  8 , Areej El-Jawahri  2 , Michael W Parsons  9
Affiliations

Long-Term Cognitive Outcomes in Adult Patients Receiving Chimeric Antigen Receptor T-Cell Therapies

Anna Barata et al. Transplant Cell Ther. 2025 Apr.

Abstract

Background: CAR T-cell therapy (CAR-T) is leading to durable responses in patients with cancer but there is concern that cytokine release syndrome (CRS) and neurotoxicity may impact survivors' cognitive function. We assessed long-term cognitive function in CAR-T recipients and examine factors associated with change in cognition over time.

Methods: We assessed perceived cognition (Functional Assessment of Cancer Therapy-Cognition) and neurocognitive performance (standardized neuropsychological battery) in adult patients prior to receiving CAR-T and at 6 month follow-up. We examined changes in cognitive outcomes using paired T-tests. We used univariate and multivariate linear regression models to explore whether patient-, disease-, or CAR-T specific factors were associated with change in cognition over time.

Results: We included 106 participants (mean age = 62.7 years, 60.4% male, 56.6% diagnosed with non-Hodgkin´s lymphoma), of whom 70 reported perceived cognition data and 26 underwent neurocognitive performance assessments at both timepoints. There were no changes in perceived cognition (P = .560), overall neurocognitive performance (P = .924), or neurocognitive domains (P´s > .05) from baseline to 6 months post CAR-T. At 6 months, 32.9% reported improved, 47.1% stable, and 20.0% declined perceived cognition relative to baseline. In unadjusted analyses, progressive disease (β = -8.86, P = .012), baseline elevated C-reactive protein (β = -5.60, P = .076) and baseline neurologic comorbidity (β = -11.4, P = .052) were numerically associated with worse perceived cognition over time. In multivariate analyses, only progressive disease was statistically significantly associated with worse perceived cognition (β = -7.32, P = .032) over time.

Conclusions: We found stable cognition among CAR-T recipients and identified an association of therapy response with change in perceived cognition over time.

Keywords: CAR-T Cell Therapy; Cognition; Multiple Myeloma; Non-Hodgkin Lymphoma; Patient-Reported Outcomes.

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Conflict of interest statement

Conflict of Interest Disclosures: PCJ-Consulting for AstraZeneca, Seagen, ADC Therapeutics, Abbvie, Incyte, Bristol Myers Squibb; Research-AstraZeneca, Incyte, Medically Home. JD: Consulting work for Amgen, Novartis, Johnson & Johnson, Janssen and SageMedic.

Figures

Figure 1.
Figure 1.
Perceived Cognition Flow Diagram
Figure 2.
Figure 2.
Percentage of participants who experienced improved, stable or worsened cognition at 6 months relative to prior to CAR-T.
See this image and copyright information in PMC

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