Axicabtagene ciloleucel

Abstract

Immune effector cell-associated neurotoxicity syndrome with acute leucoencephalomyelopathy and quadriparesis: 2 case reports In a case series of two women aged 30-41 years were described, who developed Immune effector cell-associated neurotoxicity syndrome (ICANS) manifested as acute leucoencephalomyelopathy and quadriparesis during treatment with axicabtageneciloleucel for B-cell lymphoma [route and dosage not stated]. Case 1: A 41-year-old woman, who had refractory diffuse large B-cell lymphoma and received unspecified chemotherapy. Subsequently, she underwent autologous stem cell transplantation. Her medical history was significant for bulky nodal and splenic disease. Thereafter, she received axicabtagene-ciloleucel. She experienced grade 1 cytokine release syndrome [aetiology not stated] along with fever and tachycardia from days 1 to 6. On day 2, she developed grade 3 ICANS with confusion and fever. Which resolved following treatment with tocilizumab and dexamethasone. Thereafter, her grade 3 ICANS reoccurred and on day 5 she developed grade 4 ICANS along with clonic seizures. Therefore, she received methylprednisolone along with antiepileptic drugs. However, she had generalised tonic-convulsive seizures, which were controlled with lorazepam, phenytoin, levetiracetam and phenobarbital. On day 8, as her mental status improved, she developed quadriparesis. Subsequently, her brain MRI showed findings concerning acute leucoencephalomyelopathy. By day 11, her upper extremity strength started to improve. Then, her cognitive function improved. By day 16, her lower limbs strength improved and unspecified corticosteroids treatment gradually tapered. By day 27 and 6 months, her MRI findings of the brain and spine normalised, respectively. She was able to ambulate with a walker by 6 months and eventually using a single-point cane. Case 2: A 30-year-old woman, who had refractory primary mediastinal B-cell lymphoma and received unspecified chemoimmunotherapy. She also received rituximab along with bendamustine and dexamethasone. Thereafter, she received axicabtagene-ciloleucel infusion. On day 2, she developed grade 2 cytokine release syndrome along with fever, tachycardia and hypotension. Which was treated with IV fluids, dexamethasone and tocilizumab. On day 5, she developed grade 3 ICANS, while ongoing cytokine release syndrome. Subsequently, she developed quadriparesis with complete loss of strength in both legs, nearcomplete paralysis in the upper limbs. Thereafter, she was treated with methylprednisolone along with tocilizumab, and her acute leucoencephalomyelopathy improved within few hours following administration of methylprednisolone. However, her quadriparesis lasted significantly longer. Motor deficits started to improve in the upper limbs following 2 days and recovered in the lower limbs over weeks. Her urinary incontinence resolved, however, continued to have decreased bladder sensation and a distal loss of temperature sensation. Her MRI findings were normal. She showed a partial response a month and later, a complete response.