CurrentUnitedHealthcarePolicy 2024D0077I

Gamifant (Emapalumab-Lzsg) Coverage for Primary Hemophagocytic Lymphohistiocytosis (HLH)

Defines UnitedHealthcare medical benefit coverage criteria for Gamifant (emapalumab-lzsg) for treatment of primary hemophagocytic lymphohistiocytosis (HLH), including required documentation, dosing alignment with FDA labeling, and transplant-related use limits for affected members.

Policy Summary

PayerUnitedHealthcare

PolicyGamifant (emapalumab-lzsg) coverage for primary HLH

Policy CodePolicy 2024D0077I

Change TypeNo material change

Effective DateDec 1, 2024

Next Review DateN/A

Key ActionSubmit prior authorization with supporting medical records confirming genetic diagnosis or 5 of 8 HLH criteria; dosing must follow FDA labeling and approvals are limited to 6 months.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

6 monthsmaximum approval duration

64.7%overall response (NI-0501-04)

J9210HCPCS

D76.1Diagnosis

Coverage Criteria for Gamifant (emapalumab-lzsg)

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inv-01: Initial therapy for primary HLH

Covered when ALL of the following are met

Primary HLH coverage criteria: 1) Submission of medical records confirming either a causative gene mutation known to cause primary HLH (e.g., PRF1, UNC13D) OR confirmation that 5 of the specified clinical characteristics are present (fever ≥101.3°F; splenomegaly; two cytopenias: hemoglobin <9 g/dL, platelets <100 x 10^9/L, or neutrophils <1 x 10^9/L; hypertriglyceridemia ≥265 mg/dL or hypofibrinogenemia ≤1.5 g/L; hemophagocytosis in marrow/spleen/lymph nodes without malignancy; low/absent NK cell activity; ferritin ≥500 mg/L; or soluble CD25 ≥2,400 U/ml). 2) Patient has refractory, recurrent, or progressive disease, or intolerance to conventional HLH therapy (e.g., etoposide + dexamethasone). 3) Gamifant (emapalumab-lzsg) will be administered with dexamethasone. 4) Patient is a candidate for hematopoietic stem cell transplant. 5) Gamifant is being used as part of the induction or maintenance phase prior to stem cell transplant and will be discontinued at initiation of conditioning for transplant. 6) Dosing is in accordance with FDA-approved labeling. 7) Approval is limited to no more than 6 months.

inv-02: Exclusion: Secondary HLH

Not covered / Not medically necessary

Secondary HLH: Gamifant is not proven or medically necessary for the treatment of secondary HLH.

Use of Gamifant (emapalumab-lzsg) for secondary hemophagocytic lymphohistiocytosis (secondary HLH) is not proven and not medically necessary. Documentation supporting primary HLH criteria and required treatment prerequisites must be provided for coverage; absence of primary-HLH evidence or documentation that the diagnosis is secondary HLH is a basis for denial.

Gamifant is not proven or medically necessary for the treatment of secondary HLH. Requests for emapalumab for patients with secondary HLH should be denied unless documentation demonstrates the policy’s primary-HLH coverage criteria are met.

Initial Therapy Criteria

inv-14: Initial therapy criteria

Initial approval criteria based on diagnostic confirmation and failure/intolerance to standard therapy

Initial therapy: Patient with primary HLH confirmed by genetic testing (e.g., PRF1, UNC13D) or by meeting 5 of 8 HLH diagnostic criteria (fever ≥101.3°F; splenomegaly; two cytopenias: hemoglobin <9 g/dL, platelets <100 x 10^9/L, or neutrophils <1 x 10^9/L; hypertriglyceridemia ≥265 mg/dL or hypofibrinogenemia ≤1.5 g/L; hemophagocytosis in marrow/spleen/lymph nodes without malignancy; low/absent NK cell activity; ferritin ≥500 mg/L; soluble CD25 ≥2,400 U/ml); AND refractory, recurrent, or progressive disease, or intolerance to conventional HLH therapy (e.g., etoposide + dexamethasone); AND will receive dexamethasone with emapalumab; AND is a candidate for hematopoietic stem cell transplant; AND dosing follows FDA-approved labeling; AND approval up to 6 months.

Clinical trial NI-0501-04 supports use to achieve disease control prior to transplant.

Continuation Criteria (including transplant-related rules)

inv-15: Continuation related to transplant

Continuation tied to transplant timing and overall duration limit

Continuation rules: When used as induction or maintenance in relation to hematopoietic stem cell transplant, Gamifant must be discontinued at the initiation of conditioning for transplant; overall approval is limited to no more than 6 months.6 months

Provider Actions, Authorization & Documentation

Prior Authorization

Obtain prior authorization and use correct coding

Prior authorization is required for emapalumab (J9210). Requests must include the supporting medical records described in the policy, dosing must follow FDA‑approved labeling, and approvals are limited to no more than 6 months.

HCPCS: J9210 (Injection, emapalumab-lzsg, 1 mg)
Diagnosis code: D76.1 (Hemophagocytic lymphohistiocytosis)
Approval duration: up to 6 months

Step Therapy

Confirm failure/intolerance to conventional HLH therapy

Patient must have refractory, recurrent, or progressive disease, or intolerance to conventional HLH therapy (for example, etoposide + dexamethasone) as a precondition for coverage.

Documentation Required

Provide required diagnostic documentation

Submit medical records (e.g., chart notes, laboratory values) showing either a causative gene mutation known to cause primary HLH or documentation that 5 of the specified HLH clinical criteria are present.

Examples of genetic confirmation: PRF1, UNC13D
Example clinical criteria include fever ≥101.3°F, splenomegaly, cytopenias, ferritin ≥500 mg/L, soluble CD25 ≥2,400 U/ml

Denial Risk

Secondary HLH is an exclusion — deny if sole indication

Use of Gamifant for secondary HLH is not proven or medically necessary and is a basis for denial of coverage.

Site of Care and Administration Notes

Note

No explicit site restriction — monitor infusion and infection risks

Policy does not restrict site of care to a specific infusion setting; however, infusion‑related reactions and infectious risks were observed in studies and should be considered when selecting treatment location.

Observed adverse events in studies included infusion‑related reactions (27%) and pre‑conditioning infections (56%).
Consider monitoring for bacterial, fungal, and viral infections and other serious adverse events reported during pre‑ and post‑conditioning periods.

Definitions and Diagnostic Criteria

inv-13: Diagnostic criteria for HLH (per HLH-2004)

Diagnostic pathwayDiagnosis requires either a molecular diagnosis consistent with HLH OR fulfillment of five of eight clinical criteria (per HLH-2004)

Key clinical criteria (examples)Fever (≥101.3°F), splenomegaly, cytopenias (bicytopenia defined by specified thresholds), hypertriglyceridemia or hypofibrinogenemia

Additional HLH-2004 criteriaHemophagocytosis, low/absent NK-cell activity, ferritin ≥500 mg/L, soluble CD25 ≥2,400 U/ml

Reference standardHLH-2004 (five of eight criteria unless family history/genetic test confirms HLH)

Background

Primary hemophagocytic lymphohistiocytosis (HLH) is a life‑threatening hyperinflammatory disorder for which Gamifant is indicated when specific criteria are met. This policy requires that dosing follow the FDA‑approved labeling, that treatment be administered with dexamethasone, that the patient be a candidate for hematopoietic stem cell transplant and that Gamifant be used only as part of induction or maintenance prior to transplant and discontinued at the initiation of conditioning. Approval is limited to no more than 6 months. Use of Gamifant for secondary HLH is explicitly not proven or medically necessary and is excluded from coverage.