From the Guidelines
Eculizumab is not a standard treatment for Hemophagocytic Lymphohistiocytosis (HLH) and its use is not widely recommended due to limited evidence [ 1 ].
Key Points
- The use of eculizumab in HLH is not well-established and is generally not recommended as a first-line treatment.
- 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.
- The dose and administration schedule of eculizumab for HLH are not well-defined, but it is typically used at a dose of 900 mg weekly for 4 weeks, followed by 1200 mg at week 5, and then 1200 mg every 2 weeks thereafter [ 1 ].
- Close monitoring of the patient's condition and potential side effects is essential when using eculizumab to treat HLH.
- Due to the lack of strong evidence, eculizumab should only be used under the guidance of a qualified healthcare professional and as part of a comprehensive treatment plan [ 1 ].
Considerations
- Complement-mediated disease: Eculizumab has been used in patients with complement-mediated diseases, such as C3 glomerulopathy, with variable results [ 1 ].
- Severe and refractory cases: Eculizumab may be considered in severe and refractory cases of HLH, where other treatments have failed [ 1 ].
- Terminal complement activation: Patients with evidence of terminal complement activation may benefit from eculizumab treatment [ 1 ].
From the Research
Role of Eculizumab in Treating HLH
- Eculizumab is a complement blocker that has been used in the management of thrombotic microangiopathy (TMA) in patients with hemophagocytic lymphohistiocytosis (HLH) 2.
- In a cohort of patients with therapy-refractory HLH, 10 patients received eculizumab for complement-mediated TMA management while being treated for HLH, and all patients who received eculizumab in addition to the interferon gamma blocker emapalumab had complete resolution of their TMA and survived 2.
- Eculizumab has also been used in a child with atypical haemolytic uraemic syndrome (aHUS) and haemophagocytic lymphohistiocytosis (HLH) triggered by cytomegalovirus infection, with rapid improvement in haematological and nephrological parameters 3.
Mechanism of Action
- Eculizumab binds specifically and with high affinity to the complement protein C5, thereby preventing the formation of the terminal complement complex C5b-9, which mediates cell lysis 4.
- In patients with HLH and TMA, eculizumab may help to reduce the formation of thrombi and improve organ function 2.
Combination Therapy
- Eculizumab has been used in combination with emapalumab, an interferon gamma blocker, in the treatment of HLH with TMA, with promising results 2.
- The use of eculizumab in combination with other therapies, such as plasmapheresis and immunoglobulins, may also be beneficial in the management of HLH and TMA 3.