Severe Motor Weakness Due to Disturbance in Peripheral Nerves Following Tisagenlecleucel Treatment

Abstract

Background: Neurotoxicity is one of the dangerous complications of chimeric antigen receptor (CAR) T-cell therapy, while its pathophysiology remains to be fully understood. Motor weakness not associated with central nervous system (CNS) toxicity has rarely been reported after CAR T-cell therapy.

Case report: A 42-year-old female with a refractory diffuse large B-cell lymphoma received tisagenlecleucel (tisa-cel) and developed cytokine release syndrome (CRS) on day 3. She was treated with tocilizumab and methylprednisolone, which resolved CRS promptly. On day 7, motor weakness in lower extremities appeared, and she gradually became unable to walk without showing any other symptoms attributed to CNS disturbances. Whereas dexamethasone and tocilizumab were ineffective, neuropathy improved after high dose chemotherapy followed by autologous stem cell transplantation. Nerve conduction study (NCS) in lower extremities showed a decline in compound muscle action potential amplitude along with worsening of motor weakness, which was restored after improvement of symptoms. Based on symptoms and NCS, her motor weakness was thought to be due to disturbance in peripheral nerves.

Conclusion: This study reports a patient who developed severe motor weakness due to disturbance in peripheral nerves after tisa-cel therapy. Neurotoxicity of non-CNS origin should also be noted in CAR T-cell therapy.

Keywords: Chimeric antigen receptor T-cell therapy; Tisagenlecleucel; diffuse large B-cell lymphoma; disturbance in peripheral nerves; motor weakness.