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Neurocognitive Changes After CAR T-Cell Therapy for NHL Similar to Other Cancers


With an increasing number of longer-term survivors treated with chimeric antigen receptor (CAR) T-cell therapy for non-Hodgkin lymphoma (NHL), more research is needed to confirm its effects on neurocognitive performance.

A recent study in Transplantation and Cellular Therapy is the first to the authors’ knowledge to address neurocognitive performance changes in patients with non–Hodgkin lymphoma (NHL) after CAR T-cell therapy. Neurotoxicity and cytokine release syndrome (CRS) are common in chimeric antigen receptor (CAR) T-cell therapy, but neurocognitive performance in survivors after CAR T-cell treatment has not been well researched.

CAR T-cell therapy has emerged as a revolutionary treatment in certain cancers, including relapsed or refractory hematologic malignancies. With more patents having achieved and maintained durable responses, research on longer term effects of CAR T-cell therapy in survivors is warranted.

The current study examined neurocognitive performance in patients with NHL prior to CAR T-cell therapy conditioning treatment and 30 days, 90 days, and at 1 year post treatment. Patients were eligible regardless of disease response after treatment.

A total of 117 patients with a mean age of 61 years were eligible for the study, and 87% of those patients received axicabtagene ciloleucel while the rest received tisagenlecleucel. Overall, 73% of patients responded to therapy by 90 days after infusion. Of the 54 patients who underwent neurocognitive assessment at 1 year, 71% were still showing disease response.

Neurocognitive assessments were conducted by trained research coordinators or doctoral or postdoctoral trainees in clinical psychology being supervised by a licensed clinical psychologist and neuropsychologist with expertise in assessing patients with cancer.

The overall rate of neurocognitive impairment at baseline was 33%. By day 30, this had risen to 42%, and at day 90, the rate was 48%. However, by day 360, the overall rate had decreased to 35%. The most impaired measures of neurocognitive ability were verbal ability at baseline, immediate verbal memory at day 30 post treatment, verbal ability at day 90, and delayed memory at 1 year post treatment (5%, 7%, 7%, and 4%, respectively). Total neurocognitive performance (TNP) and executive function generally decreased from baseline to day 90 before improving by day 360. There were small but significant linear visuospatial declines throughout the study period.

Demographic and clinical associations with TNP were also examined, although mixed models to assess a selection of variables—including age, gender, education, lines of prior therapy, CRS, neurotoxicity, inpatient days before day 100, and disease response at days 90 and 360—showed no significant associations with change in TNP. Given the lack of association between CRS and TNP, high levels of systemic inflammation may not be a mechanism for worse cognitive function outcomes, the authors note, adding that further research is necessary to confirm this suspicion.

Overall, patients who had undergone fewer than 4 lines of therapy prior to CAR T-cell treatment had slightly better TNP throughout the time points in the study. Additionally, those who experienced grade 2 or above neurotoxicity—but not CRS—performed slightly worse compared with patients with grade 0 or 1 throughout the study, including at baseline. The study authors note the possibility that poorer neurocognition before CAR T-cell therapy may be at a greater risk of neurotoxicity.

The rates of cognitive impairment in patients with NHL undergoing CAR T-cell therapy in this study are similar those in studies of other populations with cancer, and early screening may help identify patients who are at risk of longer-term cognitive impairment after CAR T-cell therapy, the authors concluded.

“Because neurocognitive performance after CAR T-cell therapy could change for a complex variety of reasons, we did not attempt to attribute changes to particular causal factors,” the study authors noted. “Instead, the study is intended to provide information to help educate patients and family members about what to expect after CAR T-cell therapy and identify potential supportive care needs. “


Hoogland AI, Barata A, Logue J, et al. Change in neurocognitive performance among patients with non-Hodgkin's lymphoma in the first year after CAR T-cell therapy. Transplant Cell Ther. Published online April 1, 2022. doi:10.1016/j.jtct.2022.03.023

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