CAR-T therapy has revolutionized treatment of hematologic malignancies, including MM. Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse effect of CAR-T characterized by central nervous system (CNS) symptoms typically within 2 weeks of infusion. Other neurologic adverse events after CAR-T are less well-described, particularly those involving the PNS.

Describe 6 cases of peripheral nervous system (PNS) toxicity following chimeric antigen receptor T cell (CAR-T) therapy for multiple myeloma (MM).

Six patients with refractory MM presented for B cell maturation antigen (BCMA)-targeting CAR-T therapy. All underwent lymphodepletion with fludarabine-cyclophosphamide followed by infusion with idecabtagene (patient 1) or ciltacabtagene (patients 2-6). They re-presented for new progressive sensorimotor symptoms that began after initial post-infusion monitoring period. Work-up for other infectious, autoimmune and oncologic etiologies was unrevealing. They were treated with IVIG, with corticosteroids if facial symptoms were present; outcomes were variable.

Patients 1-4 developed ascending sensorimotor symptoms and areflexia; three patients (1, 3, 4) had accompanying bilateral facial nerve involvement and autonomic symptoms. Time-to-onset of symptoms ranged from 1-6 months after CAR-T infusion. CSF albuminocytologic dissociation and/or nerve enhancement on MRI supported Guillain-Barre Syndrome (GBS) or variants; EMG/NCS in two patients (2, 3) was consistent with acute motor and sensory axonal neuropathy (AMSAN). Patients 2 and 3 partially improved over 6-12 months after IVIG. Patients 1 and 4 clinically decompensated within 2 weeks of initial IVIG treatment and died despite repeat dosing.

Patients 5 and 6 developed rapidly-progressive, isolated facial palsy 2-4 weeks post-infusion that fully resolved with corticosteroids.