Guillain-Barré syndrome after adoptive cell therapy with tumor-infiltrating lymphocytes

Abstract

BackgroundAdoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) is a promising experimental immunotherapy that has shown high objective responses in patients with melanoma. Current protocols use a lymphodepletive chemotherapy before infusion of ex vivo expanded TILs, followed by high-dose interleukin-2 (IL-2). Treatment-related toxicities are mainly attributable to the chemotherapy regimen and to the high-dose IL-2 and are generally reversible. Neurological side effects have rarely been described. Nevertheless, due to improvements in cell production techniques and due to combinations with other immunomodulating molecules, side effects not previously described may be encountered.Case presentationWe report the case of a 53-year-old heavily pretreated patient with melanoma who developed Guillain-Barré syndrome (GBS) 19 days after ACT using autologous TILs, given in the context of a phase I trial. He presented with dorsal back pain, unsteady gait and numbness in hands and feet. Lumbar puncture showed albuminocytological dissociation, and nerve conduction studies revealed prolonged distal motor latencies in median, ulnar, tibial and peroneal nerves, compatible with a GBS. The patient was treated with intravenous immunoglobulins and intensive neurological rehabilitation, with progressive and full recovery at 21 months post-TIL-ACT. Concomitant to the onset of GBS, a cytomegalovirus reactivation on immunosuppression was detected and considered as the most plausible cause of this neurological side effect.ConclusionWe describe for the first time a case of GBS occurring shortly after TIL-ACT for melanoma, even though we could not identify with certainty the triggering agent. The report of such rare cases is of extreme importance to build on the knowledge of immune cellular therapies and their specific spectrum of toxicities.

Neurotoxicity of Tumor Immunotherapy: The Emergence of Clinical Attention

“…TCR-T cell therapy-induced GBS has also been increasingly recognized. The onset of GBS-related symptoms ranges from 19 days to 142 days of TCR-T therapy initiation and shows a rapidly progressive and bilateral ascending weakness [ 24 , 92 ]. The diagnosis is mainly clinical, but may be facilitated by additional investigations, such as brain MRI, electromyography (EMG), nerve conduction studies, and lumbar puncture.…”

“…[23]. Moreover, rare complications, such as Guillain-Barre syndrome (GBS) [24][25][26][27], myasthenia gravis (MG) [28,29], cerebellar dysfunction, and aseptic meningitis have also been reported by several clinical cases. Most of these adverse effects are grade 1 or 2, but in the clinical treatment process, ≥grade 3 neurologic ir-AEs also occur in patients (the severity of ir-AEs is graded based on the Common Terminology Criteria for Adverse Events version 5.0 [30]).…”