7 Cognitive Functioning Among Patients Undergoing CAR T-Cell Therapy
Authors: Johnson Ellen E.H. , Choi Sung Won , Rozwadowski Michelle , Votruba Kristen L. 
Published: December 2023

Objective:

Chimeric antigen receptor (CAR) T-cell therapy is a novel treatment approach for refractory hematological malignancies. Risk factors for cognitive changes have been identified with CAR-T cell therapy, including severe cognitive problems due to neurotoxicity. Given the novelty of this treatment, research on this topic remains limited. Only one known study has examined cognitive performance following CAR T-cell therapy among patients diagnosed with non-Hodgkin’s lymphoma and observed a pattern of initial decline in executive functioning and visuospatial skills with improvement towards baseline one year following treatment. Additional research is needed to understand cognitive functioning in the context of CAR T-cell therapy. Our study presents preliminary descriptive longitudinal cognitive data among a small cohort of patients with mixed cancers undergoing CART cell therapy.

Participants and Methods:

Adult patients undergoing CAR T-cell therapy (N=16) completed the NIH-Toolbox core cognitive battery prior to treatment, and at 100-, 180-, and one-year post-treatment. Subtests of the Weschler Abbreviated Scale of Intelligence (WASI-II; block design, vocabulary) and the Wide Range Achievement Test (WRAT-5; word reading, math computation) were administered at baseline and one year follow up. Mean age of participants was 51.6 (SD = 14.4). Most patients had completed high school or more education (89.7%) identified as male (56.3%) and were white (75%). Diagnoses included lymphoblastic leukemia (n=2), diffuse large B-cell lymphoma (n=7), follicular lymphoma (n=3), mantle cell lymphoma (n=1), metastatic sarcoma (n=1), myxoid liposarcoma (n=1), and synovial sarcoma (n=1).

Results:

Mean cognitive scores (adjusted for age) were calculated. At baseline, mean cognitive performance was average across domains, except for inhibitory control, which was in the low average range. At day 100, mean cognitive performance showed the same pattern as baseline. At day 180, mean scores in all domains were within the average range. At one year, all scores were within the average range or higher, although only two participants have completed the one-year follow-up, as data collection is ongoing. One participant died due to neurotoxicity following treatment, thus did not complete follow-up evaluations.

Conclusions:

Overall, cognitive performances were broadly within normal limits in the sample and demonstrated relatively stable performance over time. Interestingly, baseline and day 100 mean inhibitory control was an area of relative weakness across participants, which is consistent with prior research. CAR T-cell therapy is reserved for refractory malignancies; thus, patients may have executive functioning deficits at baseline due to prior treatments. One patient died due to neurotoxicity. Overall, although severe cognitive changes and neurotoxicity have been observed as a risk of CAR T-cell therapy, this may be a distinct adverse event rather than the norm, as surviving patients in our sample remained cognitively stable following treatment. Although a unique and important population of study, our sample is limited due to its size. Results should be considered preliminary, and data collection is ongoing.