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

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.