Cytokine storms during alemtuzumab infusion: a case series

Thiago Santillan; Herval Neto; Sara Terrim; Flávio Vieira Marques Filho; Ana Beatriz Simon Nogueira; Arthur Cesário de Holanda; Rafael Augusto Rosalem; Pedro Pontes; Mariana Gondim Peixoto Spricigo; Guilherme Diogo Silva; Mateus Boaventura de Oliveira; Samira Luisa Apóstolos-Pereira; Tarso Adoni; Dagoberto Callegaro

doi:10.1055/s-0044-1789399

Arquivos de Neuro-Psiquiatria, Table of Contents

CC BY 4.0 · Arq Neuropsiquiatr 2024; 82(S 01): S1-S52
DOI: 10.1055/s-0044-1789399

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Cytokine storms during alemtuzumab infusion: a case series

Authors

Thiago Santillan

¹Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
Herval Neto

²Hospital do Servidor Público Estadual de São Paulo, São Paulo SP, Brazil.
Sara Terrim

¹Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
Flávio Vieira Marques Filho

¹Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
Ana Beatriz Simon Nogueira

¹Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
Arthur Cesário de Holanda

¹Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
Rafael Augusto Rosalem

¹Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
Pedro Pontes

²Hospital do Servidor Público Estadual de São Paulo, São Paulo SP, Brazil.
Mariana Gondim Peixoto Spricigo

¹Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
Guilherme Diogo Silva

¹Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
Mateus Boaventura de Oliveira

¹Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
Samira Luisa Apóstolos-Pereira

¹Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
Tarso Adoni

¹Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
Dagoberto Callegaro

⁴Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil.

Abstract

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Address for correspondence: Thiago Santillan (email: thiago.santillan@hc.fm.usp.br).

Abstract

Case Presentation: Alemtuzumab, a high efficacy therapy (HET) for multiple sclerosis (MS) patients in Brazil's public healthcare system, is reserved for cases where natalizumab has failed or is contraindicated due to its effectiveness. Despite being relatively common, infusion-associated reactions (IAR) with alemtuzumab are mostly mild and manageable with pre-infusion protocols involving corticosteroids, antihistamines, and analgesics. However, severe IARs can occur, posing risks to patients, yet data on clinical presentation and management remain limited. The objective of this study is to report three cases of serious adverse reactions linked to alemtuzumab infusion in MS patients. These patients were treated at two neuroimmunology clinics in São Paulo. Inclusion criteria encompassed MS patients treated with alemtuzumab infusion without contraindications. All received 12 mg of intravenous alemtuzumab, premedicated with methylprednisolone, diphenhydramine, and acetaminophen. Nursing and medical staff were trained to manage adverse effects promptly. Case 1 involved a 45-year-old female experiencing acute generalized pain, somnolence, dyspnea, and hypertensive crisis during her second infusion. Treatment was paused, and a new cycle of steroids and symptomatic drugs was initiated. Case 2, a 35-year-old male, developed acute ataxia, hypertension, and fever within two hours of infusion on the third day. The infusion was paused, and a stroke protocol was enacted to rule out vascular complications. Case 3, a 44-year-old female, presented with bilateral leg weakness and fever within two hours of infusion. Similar symptoms d during previous MS relapses were reported, yet both patients underwent a stroke protocol due to acute onset. Symptoms resolved with antipyretics.

Discussion: Suggests these IARs correspond to cytokine storm syndrome, involving release of TNF-alpha, IFN-Gamma, and IL-6, leading to fever, rash, dyspnea, and blood pressure fluctuations.

Final Comments: Infusion-associated reactions, exceeding 90%, highlight the importance of healthcare providers being vigilant regarding potential side effects associated with alemtuzumab infusion in MS treatment.