immunological parameters, neurocognitive changes, activity, & driving fitness in patients undergoing car-t cell therapy

Conditions: Hematologic Neoplasms

Summary: chimeric antigen receptor (car) t-cell therapy is a promising new treatment that re-programs patient immune cells to target and destroy cancer cells. importantly, car t-cell therapy has improved overall response rate and durability in patients with refractory or relapsed diffuse large b-cell lymphoma (dlcbl) and acute lymphoblastic leukemia (all). toxicities following car t-cell therapy remain a major limitation to expanding access to this promising cancer treatment. biological predictors of car-t-related toxicities are currently lacking, and it remains unknown whether car-t-related toxicities lead to subsequent impairments in instrumental activities of daily living. the overarching goal of this project aims to link biological predictors of car-t-related toxicities to instrumental activities of daily living, such as physical activity and driving performance. the current study proposes to test the hypothesis that car t-cell therapy causes changes in immunological and neurological markers that predict changes in physical activity levels and driving performance.

study specific aims are: (1a) evaluate changes in serum inflammatory cytokine protein markers in patients receiving car t-cell therapy; (1b) evaluate changes in electroencephalographic and radiologic markers of car-t-related toxicities in comparison to neurocognitive function following car t-cell therapy; (2a) assess changes in activity levels using actigraphy/accelerometry to continuously monitor physical activity; and (2b) assess changes in driving performance using a standardized on-road instrumented vehicle drive. patients (n=20) will be recruited into the study if they are diagnosed with relapsed or refractory dlbcl or all, and scheduled to undergo commercially-available car t-cell therapy. the following measures will be completed during primary study visits: prior to apheresis (t0) and 8-weeks post car-t cell infusion (t6). (1) blood inflammatory proteins; (2) brain wave recordings (or eeg), brain imaging, and neurocognitive assessment; (3) free-living activity levels; and (4) driving performance and safety. eeg will assess neural activity patterns of brain dysfunction; brain imaging will look for brain abnormalities; neurocognitive assessments will evaluate changes in thinking, concentration, and memory. a research-grade activity monitor will be used to assess activity levels. driving performance and safety will be evaluated using a driving simulator and an on-road vehicle designed to monitor behavior while drivers complete a driving course. analyses will assess changes between study visits, as well as relationships between immunological, neurological, activity, and driving measures.

Eligibility criteria:
inclusion criteria: 1. r/r dlbcl or r/r all diagnosis 2. scheduled to receive commercial car-t cell therapy (axi-cel or tisagenlecleucel) 3. greater than or equal to 19 years of age 4. legally licensed to drive for at least 5 years 5. previously drove an average of 50 miles/week or at least 1 hour/week 6. normal visual acuity (20/40 or better) 7. fluent in english exclusion criteria: (1) cognitive impairment (mmse score \< 21) prior to baseline assessment