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Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation. Survival of patients untreated is a few months, due to progressive multi-organ failure. Emapalumab is an interferon gamma (IFN gamma) blocking antibody. It is administered as an intravenous infusion by a health care provider.

The U.S. Food and Drug Administration (FDA) has approved emapalumab (Gamifant®) for the treatment of adult and pediatric (newborn and older) patients with primary HLH with refractory, recurrent, or progressive disease or intolerance with conventional HLH therapy. Adverse reactions have occurred in patients receiving emapalumab, including infections, hypertension, infusion-related reactions and pyrexia.

I.    Initial Review for Emapalumab (Gamifant®)

Emapalumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Diagnosis of primary hemophagocytic lymphohistiocytosis (HLH) confirmed by one of the following:
  • Confirmation of a gene mutation known to cause primary HLH; or
  • The presence of 5 of the following 8 clinical characteristics:
    • Fever
    • Splenomegaly
    • Cytopenias affecting 2 or 3 lineages in the peripheral blood:
      1. Hemoglobin <9 g/dL
      2. Platelets <100 x 10⁹/L
      3. Neutrophils <1 x 10⁹/L
    • Hypertriglyceridemia (fasting triglycerides >3 mmol/L or ≥265 mg/dL and/or hypofibrinogenemia (≤1.5 g/L))
    • Hemophagocytosis in bone marrow, spleen, or lymph nodes with no evidence of malignancy
    • Low or absent natural killer cell activity
    • Ferritin ≥500 mcg/L
    • Soluble CD25 ≥2,400 U/mL AND
• ONE of the following:
  • Inadequate response to conventional HLH therapy (cyclosporine A, dexamethasone, and etoposide); or
  • Documented intolerance, FDA labeled contraindication, or hypersensitivity to conventional HLH therapy; AND
• The drug will be used in combination with dexamethasone; AND
• For patients not currently receiving emapalumab, the patient has been screened for latent tuberculosis (TB) and started on TB therapy if the patient tests positive; AND
• No FDA labeled contraindications to emapalumab (see table 1 below); AND
• Requested dose is within the FDA labeled dose for the labeled indication (see table 2 below); AND
• For commercial health plan members only, step therapy supplement criteria may apply for select conditions (see policy II-242: Step Therapy Supplement).
  

II.   Renewal Review for Emapalumab (Gamifant®)

Emapalumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Patient has been previously approved for emapalumab through the initial review process; AND
• Demonstrated positive clinical response to emapalumab therapy (e.g., stabilization and/or slowing of disease progression, or decrease in symptom severity and/or frequency); AND
• The drug is used in combination with dexamethasone; AND
• No FDA labeled contraindications to emapalumab (see table 1 below); AND
• Requested dose is within the FDA labeled dose for the labeled indication (see table 2 below).

III.  Experimental/Investigative Uses

All other uses of emapalumab are considered EXPERIMENTAL/INVESTIGATIVE due to the lack of clinical evidence demonstrating an impact on improved health outcomes.

 Table 1. FDA Labeled Contraindications

Table 2. Dosing

NOTE: See documentation submission requirements below if the requested dose is higher or more frequent than the dosing criteria provided in this table.

Documentation Submission:

Documentation supporting the medical necessity criteria described in the policy must be included in the prior authorization, when prior authorization is required. In addition, the following documentation must also be submitted:

Initial Review

1. Clinical notes describing the diagnosis and clinical features of the diagnosis.
2. Clinical notes describing current and past medications for the diagnosis, including response to the medications.
3. The dose being requested. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
4. For commercial health plan members only, when step therapy requirements apply for the requested indication, documentation for one or more of the step therapy supplement criteria MUST be provided (see policy II-242).
   

Renewal Review

1. Documentation of prior approval for emapalumab through the initial review process.
2. Documentation supporting positive clinical response (e.g., slowing of disease progression or decrease in symptom severity and/or frequency).
3. The dose being requested. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.