Immunotherapy on ICU: a narrative review

Patients with cancer account for 15% of all admissions to critical care and so an understanding of the pathophysiology and anticipated complications of specialist treatment is essential for the intensive care clinician. The development of chimeric antigen receptor T-cell therapy for haematological malignancies and immune checkpoint inhibitors for solid organ tumours has led to significant improvements in the prognosis of those patients whose tumours respond. This review is intended to provide the non-specialist with an understanding of the current concepts in pathophysiology, diagnosis and management of complications due to chimeric antigen receptor T-cell therapy and immune checkpoint inhibitors for malignant disease.

We performed searches of electronic databases to identify relevant peer-reviewed publications in the literature. Basic science; clinical trials; cohort studies; systematic reviews; meta-analyses; and guidelines were eligible for inclusion. Abstracts were screened to identify publications relevant to immune effector cell toxicities of chimeric antigen receptor T-cell therapy and immune-related adverse events of immune checkpoint inhibitors.

While the pathophysiology for toxicities due to chimeric antigen receptor T-cells and immune checkpoint inhibitors remains incompletely understood, targeted drug therapies have been successfully implemented for toxicities such as cytokine release syndrome. Corticosteroids remain an important component of pharmacological management. The diagnosis of toxicities remains largely clinical, and a high index of suspicion should remain for infective complications. Management of toxicities should be undertaken in conjunction with the patient's primary oncologist.

Despite significant advances in the development of targeted immunotherapy, the mechanism of action for the resultant toxicities remains poorly understood and limits the development of predictive models, diagnostic biomarkers and highly effective treatment options. Further research is needed to identify treatment regimens which minimise the use of corticosteroids in chimeric antigen receptor T-cell and immune checkpoint inhibitor-associated toxicities.