Non-ICANS Neurologic Toxicity Following Anti-BCMA Chimeric Antigen Receptor T Cell-therapy: Clinical Features and Outcomes
Saira Afzal1, Faiz Anwer2, Jack Khouri2, Christy Samaras2, Raza Shahzad2, Sandra Mazzoni2, Jeffrey Cohen1, Amy Kunchok1
1Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic, 2Department of Hematology and Medical Oncology, Cancer Institute, Cleveland Clinic Foundation
Objective:
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.
Background:
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.
Design/Methods:
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.
Results:

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 10⁹/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.

Conclusions:
CNPs and MNTs following BCMA CAR-T are clinically significant. Initiation of corticosteroids, with adjunctive cyclophosphamide in MNTs may improve neurologic recovery.
10.1212/WNL.0000000000216807
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