To characterize the clinical features and outcomes of non- Immune effector cell–associated neurotoxicity syndromes (NINTs) following Chimeric Antigen Receptor T-cell (CAR-T) therapy.

In addition to Immune effector cell–associated neurotoxicity syndrome (ICANs), NINTs including cranial nerve palsies (CNPs) and movement/neurocognitive toxicities (MNTs) have been increasingly reported with CAR-T therapy.

In this retrospective cohort study, adults who developed CNPs or MNTs associated with CAR-T therapy at Cleveland Clinic were identified. Clinical and imaging features, treatment, and outcomes are described.

11 patients were identified (64% male, median age 70 years, range 57–76), all treated with BCMA-directed CAR-T (ciltacabtagene autoleucel) for multiple myeloma. Presentations included isolated MNTs (4, 36%), CNPs (5, 45%), combined MNT+CNP (1, 9%), and CNP with peripheral neuropathy (1, 9%).

Symptom onset was at median 22 days (range 13–57). MNTs (n=5) manifested rigidity (5), resting tremor (5), bradykinesia (3), masked facies (3), postural/gait change (2), and cognitive impairment (4). Only 1 demonstrated abnormal MRI findings; bilateral non-enhancing T2/flair hyperintensities in basal ganglia (resolved on repeat MRI 22 days later). CNP cases involved unilateral CN VII (5), CN VI (1) and CN VI &VII (1); one MRI showed enhancement of facial nerve. CSF (n=2) showed pleocytosis with elevated protein (1) and elevated IgG index (1). Median absolute lymphocyte counts at weeks 1,2,3 and 4 were 0.11, 4.75, 1.23, and 0.67 x 10?/L, respectively. Median M-protein was 0.18 g/dL at baseline.

MNTs treatment included corticosteroids and dopaminergic therapy (1), cyclophosphamide and corticosteroids (2) and dopaminergic therapy only (2). Improvement was seen in 3 MNTs; complete resolution (1); treated with corticosteroids plus cyclophosphamide. Partial improvement (2); treated with cyclophosphamide (1), carbidopa-levodopa (2). All CNPs received corticosteroids and showed improvement.

CNPs and MNTs following BCMA CAR-T are clinically significant. Initiation of corticosteroids, with adjunctive cyclophosphamide in MNTs may improve neurologic recovery.