Medium-Term Cognitive Outcome in Patients With CNS Lymphomas Treated With Chimeric Antigen Receptor T-Cell Therapy

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated promising efficacy results in CNS lymphomas, with reassuring rates of acute neurotoxicity. However, the neurologic outcome of these brain-injured patients remains unknown beyond the short term. Our objective was to report on the medium-term neurocognitive evolution.

We retrospectively selected isolated CNS lymphomas treated with CAR T cells (June 2021-April 2024) at Pitié-Salpêtrière Hospital who had neuropsychological follow-up as part of routine care (various tests evaluating main cognitive domains: language, memory, executive functions, visuospatial abilities, and overall functioning). We collected the results of the various cognitive tests from the patients' medical records at baseline, in the absence of tumoral progression; 6 weeks (W6); 6 months (M6); and 12 months (M12) after CAR T-cell therapy. We used paired Student t tests to compare follow-up values of neurocognitive variables with their baseline values. The primary outcome was the difference in Montreal Cognitive Assessment (MoCA) scores between baseline and M12.

Thirty patients (43% female, 57% male) were included, of whom 21 had neuropsychological assessment up to M12. Their median age was 61 years (range 30-82). At baseline, MoCA score was 23.5 (range 11-29) and 34%-80% of patients had abnormal scores in the main cognitive domains. Nineteen (63%) patients experienced acute neurotoxicity (6 (20%) of grade ≥3). Twenty-one patients (70%) maintained or improved their MoCA score at W6, while 9 (30%) worsened theirs. The occurrence and severity of neurotoxicity were significantly associated with these 2 types of initial trajectories (p = 0.003, 95% CI 1.78-1,227.01). There was a significant improvement of MoCA score at M6 (mean 24.7 vs 22.6, p = 0.002, 95% CI 0.92-3.37) and M12 (mean 25.4 vs 22.1, p < 0.001, 95% CI 2.12-4.92) compared with baseline. Language score significantly improved between baseline and M12 (mean Z-score of -0.6 vs -0.1; p = 0.02, 95% CI 0.08-0.9). Scores addressing memory, executive functions, visuo-spatial functions, and anxiety/depression were stable or improved, although not significantly.

Midterm neurocognition follow-up in patients with CNS lymphoma treated by CAR T cells seems reassuring, with no significant cognitive worsening, and even an improvement in general cognitive functioning, even in patients who experienced severe acute neurotoxicity. These results should be confirmed with longer follow-up.