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

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=0.560), overall neurocognitive performance (p=0.924), or neurocognitive domains (p´s >0.05) 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=0.012), baseline elevated C-reactive protein (β= -5.60, p=0.076) and baseline neurologic comorbidity (β= -11.4, p=0.052) 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=0.032) 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.