Table 5

Treatment recommendations for ECD patients

TherapyTreatmentDose and scheduleLevel of recommendation*Comment
Clinical trial (first or second-line treatment) Vemurafenib (NCT01524978) 480-960 mg PO twice daily† Grade C2 Dramatic efficacy described in 3 cases81  and anecdotal experience with off-label use are known. Enrollment in prospective clinical trial is essential to document efficacy and potential toxicities as well as determine duration of therapy. 
 Tocilizumab (NCT01727206) Per clinical trial guideline Grade C2 Phase II clinical trial of this anti-IL6 antibody in ECD is underway based on rationale of systemic elevation of IL-6 documented in ECD patients.14  
 Sirolimus and prednisone (ACTRN12613001321730) Per clinical trial guideline Grade C2 Prospective trial underway based on concept of interfering with immune dysregulation in ECD. Moreover, recent identification of activating RAS mutation in ECD12  may provide rationale for mTOR inhibition by sirolimus in certain ECD patients. 
First-line PEG-IFNα15  135 μg SC/wk (standard dose) or 180 μg SC/wk (high dose) Grade C2 Currently the therapy with largest clinical evidence-base in ECD.59-62  Case series have demonstrated survival benefit with the use of some form of IFN-α.45  High-dose IFN-α ended for patients with CNS or cardiac involvement.61  
 IFN-α15  3 mIU SC TIW (standard dose) or 6-9 mIU SC TIW (high dose) Grade C2 Optimal duration of therapy unknown but use up to 3 y has been described.62  
 Anakinra65,98  100 mg SC daily Grade C1 A single case series describes efficacy of anakinra in treatment of constitutional symptoms in ECD.64-66  Appears to be less efficacious than IFN-α for therapy of patients with CNS or cardiac involvement. 
Second-line Cladribine3,77  6 mg/m2 IV daily for 5 days every 4 wks Grade C1 Used frequently in clinical therapy of systemic LCH and ECD, but published reports of its efficacy are few. 
 Imatinib83,85,99  400 mg PO daily Grade C0 Results in 7 ECD patients treated with imatinib have been mixed, although it appears that it may be more effective in less advanced or severe forms of the disease.84,85  
 Infliximab68  5 mg/mg IV every 6 wks Grade C1 Four patients with cardiac disease refractory to treatment with IFN-α had clinical improvement when treated infliximab.68,100  
TherapyTreatmentDose and scheduleLevel of recommendation*Comment
Clinical trial (first or second-line treatment) Vemurafenib (NCT01524978) 480-960 mg PO twice daily† Grade C2 Dramatic efficacy described in 3 cases81  and anecdotal experience with off-label use are known. Enrollment in prospective clinical trial is essential to document efficacy and potential toxicities as well as determine duration of therapy. 
 Tocilizumab (NCT01727206) Per clinical trial guideline Grade C2 Phase II clinical trial of this anti-IL6 antibody in ECD is underway based on rationale of systemic elevation of IL-6 documented in ECD patients.14  
 Sirolimus and prednisone (ACTRN12613001321730) Per clinical trial guideline Grade C2 Prospective trial underway based on concept of interfering with immune dysregulation in ECD. Moreover, recent identification of activating RAS mutation in ECD12  may provide rationale for mTOR inhibition by sirolimus in certain ECD patients. 
First-line PEG-IFNα15  135 μg SC/wk (standard dose) or 180 μg SC/wk (high dose) Grade C2 Currently the therapy with largest clinical evidence-base in ECD.59-62  Case series have demonstrated survival benefit with the use of some form of IFN-α.45  High-dose IFN-α ended for patients with CNS or cardiac involvement.61  
 IFN-α15  3 mIU SC TIW (standard dose) or 6-9 mIU SC TIW (high dose) Grade C2 Optimal duration of therapy unknown but use up to 3 y has been described.62  
 Anakinra65,98  100 mg SC daily Grade C1 A single case series describes efficacy of anakinra in treatment of constitutional symptoms in ECD.64-66  Appears to be less efficacious than IFN-α for therapy of patients with CNS or cardiac involvement. 
Second-line Cladribine3,77  6 mg/m2 IV daily for 5 days every 4 wks Grade C1 Used frequently in clinical therapy of systemic LCH and ECD, but published reports of its efficacy are few. 
 Imatinib83,85,99  400 mg PO daily Grade C0 Results in 7 ECD patients treated with imatinib have been mixed, although it appears that it may be more effective in less advanced or severe forms of the disease.84,85  
 Infliximab68  5 mg/mg IV every 6 wks Grade C1 Four patients with cardiac disease refractory to treatment with IFN-α had clinical improvement when treated infliximab.68,100  

PO, by mouth; SC, subcutaneous.

*

Grade and level of recommendation definitions are listed in Table 1.

†

960 mg twice daily is the FDA-approved dose of vemurafenib for melanoma; however, anecdotally, in most ECD patients, 480 mg twice daily is better tolerated and has been efficacious.

View Large