Reader Response: Long-term Neurologic Safety in Patients With B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

We read this article with interest.¹ The potential long-term neurologic sequalae and, in particular, cognitive impairment following CAR T-cell therapy are receiving greater attention given the treatment's increasing availability and use.

Despite the small sample size, we think Ursu et al.¹ have covered some of the key deficiencies of current published studies on the topic, which are often limited by a short follow-up period, lack of systemic neuropsychological evaluations, and no baseline or follow-up neuroimaging data. They report that CAR T-cell therapy does not have an adverse impact on cognitive functions for up to 2 years in relatively well lymphoma patients who had minimal acute neurotoxicity in the first few weeks of treatment.

Unlike several other studies, these authors have utilized a fairly comprehensive assessment of different cognitive domains. Two other recent studies that used extensive neuropsychological tests have produced similar findings.^2,3 In a 2-year study, Shalabi et al. found that the majority of their 22 patients had stable or improved cognitive test scores following the therapy² while Maillet et al.³ involved a trained neuropsychologist to administer 5 cognitive domain tests and found no cognitive impairment in their patients 6–12 months after therapy.

While it may be premature to draw definitive conclusions on the long-term effect of CAR T-cell therapy on cognitive functions due to methodological differences and patient heterogeneity, we think future studies with detailed neuroimaging sequences that can correlate any changes in objective neuropsychological tests will provide clarity on this issue.