The goal of CRS management is to minimise life-threatening toxicity while maintaining the antitumour effects of treatment.r
Low grade CRS
Symptomatic treatment with antihistamines, antipyretics and fluids is recommended. Additional diagnostic testing should be performed and antibiotic therapy should be considered if an infection cannot be ruled out.rr
Severe CRS represents a life-threatening situation that requires immediate and aggressive treatment.r Patients with severe CRS should be treated in the ICU to enable continuous monitoring, management of life-threatening arrhythmias, haemodynamic shock, non-invasive positive pressure ventilation, mechanical ventilation, and/or dialysis.r Treatment strategies include Tocilizumab and corticosteroids.
Tocilizumab can be accessed via a Special Access Scheme for this indication.
Tocilizumab, a recombinant humanised monoclonal antibody is effective treatment for severe or life-threatening CRS. Tocilizumab prevents IL-6 from binding to both cell-associated and soluble IL-6 receptors.rr Patients that develop grade 3 or 4 CRS toxicity should immediately receive treatment with tocilizumab. Generally, significant resolution of CRS related symptoms e.g. fever and hypotension is achieved within a few hours up to two days after the first dose of tocilizumab. If symptoms do not subside within 24 to 72 hours a second dose is feasible.r
Note: Post administration of tocilizumab, CRP can no longer be used as an indicator of CRS severity as blockade of IL-6 signaling results in a rapid decrease of CRP.r
Corticosteroids are an obvious choice to blunt CRS owing to their efficacy in muting inflammatory processes. Indeed, corticosteroids have been incorporated into the supportive care for blinatumomab therapy to reduce the incidence of severe CRS. Despite this, corticosteroids should be avoided as first line treatment in patients receiving CAR-T cell therapy due to the potential negative impact on therapeutic T cell proliferation and thus efficacy of treatment. It is recommended that corticosteroids are reserved for cases refractory to IL-6 blockade or severe neurotoxicity.rr