Is Eculizumab used for Hemophagocytic Lymphohistiocytosis (HLH)?

From the Guidelines

Eculizumab is not a standard treatment for Hemophagocytic Lymphohistiocytosis (HLH) and its use is not widely recommended due to limited evidence. However, in certain severe and refractory cases, eculizumab may be considered as a potential therapeutic option to manage HLH, particularly in patients with evidence of terminal complement activation, as seen in some cases of immune-related adverse events 1.

Key Considerations

• The recommended dose is typically 900 mg weekly for 4 weeks, followed by 1200 mg at week 5, and then 1200 mg every 2 weeks thereafter, as suggested for the management of immune-related adverse events 1.
• Close monitoring of the patient's condition and potential side effects is essential, given the lack of strong evidence supporting the use of eculizumab in HLH.
• Due to the limited evidence, eculizumab should only be used under the guidance of a qualified healthcare professional and as part of a comprehensive treatment plan.

Treatment Alternatives

• Other treatment options for HLH include immunoglobulins, glucocorticosteroids, cyclosporin A, and etoposide (VP16), as outlined in the HLH-94 and HLH-2004 protocols 1.
• Anti-interleukin-1 treatment may be used for HLH in auto-inflammatory conditions, in addition to glucocorticosteroids, cyclosporin A, and etoposide 1.

Important Notes

• The diagnosis and management of HLH can be challenging, particularly in adults, due to the heterogeneity of the disease and the lack of validated diagnostic criteria 1.
• A comprehensive treatment plan should take into account the underlying trigger of HLH, as well as the patient's overall clinical condition and potential comorbidities.

From the Research

Eculizumab Use in Hemophagocytic Lymphohistiocytosis (HLH)

• Eculizumab is used in the management of thrombotic microangiopathy (TMA) in patients with HLH, as seen in a study published in the Journal of Clinical Immunology 2.
• The study found that patients with HLH and TMA who received eculizumab had complete resolution of their TMA and survived.
• Another case report published in BMJ Case Reports describes the use of eculizumab in a child with atypical haemolytic uraemic syndrome (aHUS) and HLH triggered by cytomegalovirus infection 3.
• In this case, eculizumab was effective in treating aHUS, despite the presence of a comorbid immunological disease.
• However, it is essential to note that eculizumab is not a primary treatment for HLH, but rather used to manage associated conditions like TMA.
• The primary treatment for HLH involves immunosuppressive and cytotoxic drugs, as well as hematopoietic stem cell transplantation (HSCT) in primary HLH, with emapalumab being a targeted therapy approved for primary HLH with refractory, recurrent, or progressive disease 4.

Mechanism of Action and Indications

• Eculizumab is a humanized monoclonal antibody that binds specifically to the complement protein C5, preventing the formation of the terminal complement complex C5b-9, which mediates cell lysis 5.
• Its primary indication is for the treatment of paroxysmal nocturnal haemoglobinuria (PNH), where it inhibits terminal complement-mediated intravascular haemolysis.
• The use of eculizumab in HLH is off-label and based on its mechanism of action in managing TMA, which can be a complication of HLH.