Molecular Evidence (rationale) for IL-1 targeted therapy in iMCD patients:

  • IL-1 is frequently elevated in iMCD. “IL-1, which is upstream of IL-6 in the proinflammatory cascade and leads to IL-6 production through nuclear factor (NF)-kB signaling, was expressed at elevated levels in 5 cases of HHV-8-unknown MCD.” (Blood 2014)
  • “Additionally, a patient who did not respond to anti-IL-6 therapy had complete response to anti-IL-1 therapy in 1 case report” (Blood 2014)

Case Reports of anti-IL-1 therapy for iMCD patients:

Anakinra (Kineret) is an IL-1 receptor monoclonal antibody (mAb) or an IL-1 receptor antagonist. Three iMCD patients (two pediatric and one adult) treated with anakinra have been published in case reports. Two patients achieved complete response to anakinra and one patient achieved a partial response. See patient descriptions below.

  • 6.5-year-old male with iMCD had partial response to 2nd-line anakinra for 27 months without relapse. Prior treatment of rituximab and cytotoxic chemotherapy (cyclophosphamide, vinblastine) for 5 months achieved no response. At 16.5 years old, 3rd-line tocilizumab achieved 36 months complete remission without relapse. (Galeotti et al)
  • 13-year-old male with mixed-type iMCD received 2nd-line therapy of anakinra plus corticosteroids (and colchicine) with complete remission for 18 months without relapse (all clinical symptoms resolved except had occasional fevers for 6 months, decreased lymph node size, CRP waxed and waned, and hemoglobin, ESR, and immunoglobulin levels stabilized). Prior therapy of rituximab plus cytotoxic chemotherapies (cyclophosphamide, vinblastine) achieved partial response for 7 months. (Galeotti et al)
  • 61-year-old female with iMCD resistant to multiple treatments achieved 7 months complete remission on 5th-line anakinra. Previous treatments included 1st-line siltuximab with partial remission (improved blood counts, lymphadenopathy resolved, but intermittent fever and rash persisted) for 36 months; 2nd-line corticosteroids and etanercept with no response; 3rd-line consecutive plateletpheresis for thrombocytosis and then cladribine for 5 days with no response, then repeated courses of steroids and later naprosyn for possible neoplastic fever; 4th-line was weekly dose of rituximab for 8 weeks, with persistence of disease flare up, at which point she was started on anakinra. (El-Osta et al)

Clinical Trials targeting IL-1 in iMCD:

No clinical trials targeting IL-1 in iMCD patients have been conducted. Some insurance companies will approve anakinra to iMCD patients if it is prescribed by a physician.

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