7032 Background: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the management of relapsed and refractory hematologic malignancies, challenging the established role of autologous stem cell transplantation (ASCT). However, the chronic neurocognitive effects of CAR-T therapy remain unclear. This study compares the long-term risk of cognitive impairment between CAR-T and ASCT therapy recipients. Methods: We conducted a retrospective cohort study using US hospital data from the TriNetX research network. Patients exclusively receiving either CAR-T therapy or ASCT were propensity score-matched 1:1 and adjusted for age, sex, primary cancer diagnosis, major comorbidities, neuropsychiatric comorbidities, dexamethasone use, and laboratory values (BMI, LDH if available). Participants with prior cognitive impairment diagnosis within 1 year before index or who received multiple treatment modalities during the study period were excluded. The primary endpoint was time-to-event cognitive impairment, defined by ICD-10 codes for mild cognitive impairment, memory loss, and difficulty with concentration. Secondary outcomes included time to neurological dysfunction (delirium, encephalopathy, seizures), mood and stress-related disorders (depression, anxiety, sleep disorder), fall-related injuries, mobility impairment, and secondary malignancies. Results: After propensity score matching, 3,067 CAR-T patients were compared with 3,067 ASCT patients. CAR-T recipients demonstrated a 58% higher risk of cognitive impairment (HR 1.583; 95% CI 1.390-1.80) and a 57% higher risk of neurological dysfunction (HR 1.567; 95% CI 1.403-1.751) compared to ASCT patients. Encephalopathy was the most prominent individual complication, with CAR-T patients showing a 2-fold higher hazard compared to ASCT patients (HR 2.035; 95% CI 1.727-2.398). To account for acute ICANS, events occurring within the first 7 days were excluded, and CAR-T patients maintained higher hazard of cognitive impairment (HR 1.695; 95% CI 1.466-1.959). The risk was highest within the first 30 days (HR 4.224; 95% CI 3.227-5.528) and remained persistently elevated throughout the follow-up period, even at 2500 days (HR 1.761; 95% CI 1.535- 2.021). Among CAR-T products, ciltacabtagene autoleucel showed the highest hazard (HR 2.013; 95% CI 1.092-3.708), while tisagenlecleucel showed the lowest (HR 1.530; 95% CI 1.030-2.271). All p<0.001. Conclusions: Compared to ASCT, CAR-T cell therapy was associated with a significantly increased risk of long-term cognitive impairment and neurological dysfunction. These findings have important implications for incorporating neurocognitive assessment into treatment discussion, informed consent, and the need for long-term monitoring.
Sun et al. (Wed,) studied this question.