211 - Critical Illness Polyneuromyopathy Following CAR-T Cell Therapy: A Case Report

Case Diagnosis: A 68-year-old male with diffuse large B-cell lymphoma developed critical illness polyneuromyopathy following CAR-T cell therapy

Case Description: A 68-year-old male diagnosed with diffuse large B-cell lymphoma underwent CD19-directed CAR-T cell infusion. After one week, he developed cytokine release syndrome and neurotoxicity, treated with corticosteroids and tocilizumab. His hospital course was complicated by septic shock due to bacteremia, respiratory failure, renal failure, and hypotension, requiring a prolonged ICU stay. He developed weakness, neuropathy, tremors, and encephalopathy. Cerebrospinal fluid analysis was negative for anti-CD19 CAR-T cells but showed elevated IL-6 levels. Electrophysiology confirmed an axonal sensorimotor polyneuropathy, consistent with critical illness polyneuromyopathy. He began inpatient rehabilitation and demonstrated gradual gains but required multiple rehabilitation admissions due to recurrent medical setbacks. At follow-up, he remained independent in most activities of daily living with outpatient therapy support, while ongoing physiatry and neurology follow-up were recommended to address long-term motor and cognitive complications.

Discussions: CAR-T therapy often causes cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), with neurological symptoms reported in ~40.8% of patients. Common manifestations include encephalopathy, language disturbance, and seizures. Treatment for CSR includes tocilizumab and corticosteroids, which mitigate the cytokine surge, reducing inflammation and potentially lessening the severity of critical illness polyneuromyopathy.
In this case, systemic complications such as septic shock and multi-organ dysfunction further impaired outcomes. Electrophysiology supported the diagnosis of critical illness polyneuromyopathy. Persistent deficits highlight the need for ongoing neurology involvement, while rehabilitation medicine remains central to functional recovery, often requiring repeated admissions for complex CAR-T survivors.

Conclusions: CAR-T therapy can lead to prolonged neuromuscular and cognitive complications. This case highlights the importance of early recognition, repeated rehabilitation, and sustained neurologic follow-up. Multidisciplinary care remains essential for maximizing recovery and addressing persistent adverse effects of CAR-T-related neurotoxicity.