From the Guidelines
Refractory Hemophagocytic Lymphohistiocytosis (HLH) treatment should be escalated to emapalumab, an anti-IFN-γ antibody, in patients with severe disease and inadequate response to high-dose glucocorticoids (GCs), as it has shown significant efficacy in achieving MAS remission with a marked GC sparing effect and a reassuring safety profile 1.
Treatment Options
The treatment of refractory HLH involves the use of various immunosuppressive agents, including:
- Emapalumab, which has been tested in a clinical trial and shown to be effective in achieving MAS remission 1
- Ciclosporin, which can be considered in case of inadequate response to GCs, particularly in less resourced countries 1
- Anakinra, which has been used in real-world experience in MAS, at doses higher than the standard 1 to 2 mg/kg/day, and possibly in intravenously repeated doses 1
- JAK inhibitors, such as ruxolitinib or baricitinib, which have shown efficacy in a few case reports 1
- Low-dose etoposide, which may also be considered in refractory MAS 1
Combination Therapies
Combination therapies with multiple agents on a background of high-dose GCs are often necessary and should be considered as initial therapy, particularly in patients with severe MAS and rapid worsening 1. The choice of treatment or combination therapy should be discussed with experts of a reference centre, taking into account the higher mortality of patients with MAS reported in adults.
Key Considerations
The goal of therapy is to rapidly suppress the hyperinflammatory state while addressing any underlying triggers that may be driving the HLH process. Urgent consideration for allogeneic hematopoietic stem cell transplantation (HSCT) is essential for patients with refractory HLH, as this represents the only curative option, particularly for genetic or persistently active disease.
From the Research
Treatment Options for Refractory Hemophagocytic Lymphohistiocytosis (HLH)
The treatment options for refractory HLH include:
- Salvage or alternative therapeutic approaches for patients who fail to achieve remission with established regimens, such as dexamethasone and etoposide, or methylprednisolone and antithymocyte globulin (ATG) 2
- Corticosteroids, etoposide, cyclosporine A, alemtuzumab, and ATG for CNS-HLH, as well as intrathecal treatment with methotrexate and corticosteroids 3
- Allogenic hematopoietic stem cell transplantation (HSCT) for patients with primary HLH, even if there is active disease at the time of transplantation 3
- Novel approaches, such as anti-IFN-gamma antibody (NI-0501), which is currently being tested 3
- DEP regimen and allogenic HSCT, which are associated with complete response and partial response in 27% and 49.2% of patients, respectively 4
- New drugs, such as emapalumab, ruxolitinib, and alemtuzumab, which may be used as bridges to curative HSCT and have shown promising results in terms of response rates and survival 4
- Chemo-immunotherapy and cytokine-targeting biologicals, which are more effective in eliminating pathologically activated T cells and resisting exaggerated cytokine storms 5
- Alemtuzumab, which has been used to treat HLH due to systemic lupus erythematosus and has shown promising results 6
Key Considerations
- The treatment of HLH should be individualized based on the underlying trigger, disease severity, and genetic background 5
- A uniform protocol and algorithm for the treatment of HLH may not be appropriate for each patient due to the heterogeneity of the underlying conditions 5
- Further improvements in therapy require prospective trials to develop reasonable strategies for HLH patients in different subtypes 5