Blue Cross Blue Shield MA interferons Prior Auth

Coverage Criteria

FDA‑approved Interferon alpha indications

Covered when meeting FDA‑approved uses or as specified below

FDA-approved Interferon alpha uses: Genital warts (condylomata acuminata); Kaposi's sarcoma; Chronic hepatitis B; Acute or chronic hepatitis C; Malignant melanoma.

From Clinical Coverage Criteria: Interferon alpha.

Off‑label Interferon alpha indications (MA mandate)

May cover selected off‑label uses (prior authorization required)

Off-label interferon alpha uses (MA USP mandate): Chronic Myelogenous Leukemia (CML) given alone as first-line therapy for patients in the first chronic phase; Multiple myeloma as first-line in combination with cytotoxic agents and as maintenance in previously responsive patients; Polycythemia vera; Idiopathic progressive polyneuropathy; HIV/AIDS; Selected cancers listed in the United States Pharmacopeia (e.g., bladder, renal/kidney, cervix, brain, colorectal, head and neck, ovary, pancreas, bone/osteosarcoma) and certain skin cancers (including malignant melanoma, mycosis fungoides, cutaneous T-cell lymphoma); recurrent respiratory/laryngeal papillomatosis; chronic lymphocytic leukemia; carcinoid syndrome.Prior authorization required

Massachusetts mandate: off‑label USP-listed cancer indications may be considered but evidence for some cancer uses is mixed and prior authorization is required.

Sylatron — adjuvant melanoma

Covered when ALL of the following are met

Sylatron (peginterferon alpha-2b) — adjuvant melanoma: Adjuvant treatment of melanoma with microscopic or gross nodal involvement; initiated within 84 days of definitive surgical resection, including complete lymphadenectomy.Initiation within 84 days of definitive surgical resection

Specific postoperative time window required for coverage.

Interferon gamma (Actimmune) covered indications

Interferon gamma coverage

Actimmune (interferon gamma) covered uses: Chronic Granulomatous Disease to reduce frequency and severity of infections; Severe malignant osteopetrosis (SMO) to delay time to disease progression.

Conditions not listed are not covered due to insufficient evidence of improved health outcomes.

We do not cover interferon gamma (Actimmune) for indications beyond its FDA‑approved uses. Coverage is limited to the FDA‑approved indications listed in this policy — Chronic Granulomatous Disease (to reduce frequency and severity of infections) and to delay progression of severe malignant osteopetrosis. Conditions not listed are not covered due to insufficient scientific evidence demonstrating improved health outcomes.

Selected off‑label cancer uses of interferon alpha are noted in this policy under the Massachusetts USP mandate and may be considered for coverage only with prior authorization. The policy specifies numerous malignancies (for example: bladder, renal, cervix, brain, colorectal, head and neck, ovary, pancreas, osteosarcoma, malignant melanoma, mycosis fungoides/cutaneous T‑cell lymphoma, and others) but also states that for some of these cancers the evidence does not show improved health outcomes and may worsen quality of life; therefore documentation supporting medical necessity must be submitted and requests may be denied if criteria are not met.

Initial Therapy Criteria

Off‑label initial therapy

Off‑label uses considered for initial authorization (prior authorization required)

Off-label initial therapy — general rules: Requests for off-label initial therapy with interferon products (including USP-listed cancer indications and the off‑label hematologic/neurologic uses listed) require prior authorization with supporting clinical documentation describing diagnosis, prior treatments and responses, and rationale for interferon use.Prior authorization required

Policy states prior authorization is required for off‑label uses; providers should submit clinical notes and evidence to support requests.

Hepatitis C therapy context

Therapeutic context — historical standard for chronic hepatitis C

Hepatitis C therapy context: Clinical trials and reviews establish pegylated interferon combined with ribavirin (peginterferon + ribavirin) as the historical standard regimen for chronic hepatitis C in the cited literature; this context informs expected therapeutic sequencing and treatment regimens when interferon-based therapy is used.

Coding

HCPCS CodesHCPCS

J9212	Injection, interferon Alfacon-1, recombinant, 1 mcg (Infergen)
J9214	Injection, interferon, alfa-2b, recombinant, 1 million units (Intron A, Rebetron Kit)
J9215	Injection, interferon, alfa-N3, (human leukocyte derived), 250,000 IU (Alferon N)
J9216	Injection, interferon, gamma 1-b, 3 million units (Actimmune)

ICD-10 Diagnosis Codes (partial list shown)ICD-10

A63.0	Anogenital (venereal) warts
B17.10	Acute hepatitis C without hepatic coma
B18.2	Chronic viral hepatitis C
B20	Human immunodeficiency virus [HIV] disease
C43.0	Malignant melanoma of lip

Listed ICD-10 Diagnosis CodesICD-10Covered

C44.121	Basal cell carcinoma of skin of left lower eyelid, including canthus.
C44.1221	Squamous cell carcinoma of skin of unspecified eyelid, including canthus.
C44.1222	Squamous cell carcinoma of skin of right upper eyelid, including canthus.
C44.1291	Squamous cell carcinoma of skin of right lower eyelid, including canthus.
C44.1292	Squamous cell carcinoma of skin of left upper eyelid, including canthus.
C44.131	Squamous cell carcinoma of skin of left lower eyelid, including canthus.
C44.1321	Sebaceous cell carcinoma of skin of unspecified eyelid, including canthus.
C44.1322	Sebaceous cell carcinoma of skin of right upper eyelid, including canthus.
C44.1391	Sebaceous cell carcinoma of skin of right lower eyelid, including canthus.
C44.1392	Sebaceous cell carcinoma of skin of left upper eyelid, including canthus.

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Provider Actions and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior Authorization is required for medications covered by this policy. Requests should be submitted to Blue Cross Blue Shield of Massachusetts Pharmacy Operations; specialty drugs may be required to be filled through the BCBSMA retail specialty pharmacy network when obtained under the pharmacy benefit. See contact: Pharmacy Operations: Tel: 1-800-366-7778, Fax: 1-800-583-6289.

Prior Authorization required for listed medications
Specialty pharmacy routing may apply for pharmacy benefit fills
Pharmacy Operations: 1-800-366-7778 / Fax: 1-800-583-6289

Denial Risk

Diagnosis-code Requirement

Claims and prior authorization requests must include a diagnosis code from the ICD-10 codes enumerated in this policy. Absence of an appropriate listed diagnosis code may result in denial of the request or claim.

Site of Care / Dispensing

Billing Rule

Specialty pharmacy dispensing and site‑of‑care requirements

Medications designated as specialty and covered under the pharmacy benefit must be dispensed through BCBSMA’s retail specialty pharmacy network when obtained via the pharmacy benefit; contact Pharmacy Operations or consult the specialty pharmacy link for network providers.

BCBSMA requires specialty‑designated medications to be filled at retail specialty pharmacy providers listed in the BCBSMA specialty pharmacy network.
Members filling specialty drugs via the pharmacy benefit (not medical benefit) must use the specialty network per policy instructions.

Step Therapy and Utilization Controls

Coverage Control	Policy Note
Prior Authorization	Prior authorization is required for listed interferon products on the BCBSMA formulary; specialty pharmacy routing applies where indicated.
Step therapy	Step therapy is not specified as a required utilization control in this policy; the primary controls are prior authorization and Quality Care Dosing.
Quality Care Dosing	Quality Care Dosing requirements apply as indicated in policy (refer to related Quality Care Dosing guidelines and pharmacy operations contact information).

Drug / Regimen	Typical trial dosing and duration (context from cited studies)
Interferon alfa-2b ± ribavirin	Interferon alfa-2b used alone or in combination with ribavirin; trials cited include Davis et al. and McHutchison et al. evaluating interferon alfa-2b with ribavirin as initial or relapse therapy for chronic hepatitis C (late 1990s).
Pegylated interferon (alfa-2a or alfa-2b) + ribavirin	Multiple randomized trials of pegylated interferon plus ribavirin are cited (e.g., Lindsay et al., Reddy et al., Hadziyannis et al., Fried et al.); studies evaluated peginterferon regimens and compared dosing, duration, and ribavirin dose to optimize sustained response. Specific trials include dose-ranging and duration comparisons (see references).
Peginterferon dose-ranging studies	Dose-ranging and randomized studies (Glue et al., Hepatitis C Intervention Therapy Group; Hadziyannis et al.) assessed peginterferon dosing and treatment duration, informing historical standard regimens used in hepatitis C therapy.

Definitions

Interferon gamma (Actimmune) — key facts

Drug nameActimmune (interferon gamma-1b)

Covered indications (FDA)Chronic Granulomatous Disease — to reduce frequency and severity of infections; Severe malignant osteopetrosis — delay time to disease progression.

Coverage stanceCovered only for FDA-approved uses; other conditions are not covered due to insufficient evidence.

Notes to providersEnsure claims link to an appropriate listed ICD-10 diagnosis code supporting the FDA indication to avoid denial.

Infergen (interferon alfacon-1) — historical/endnote note

ProductInfergen (interferon alfacon-1)

Background

Interferon products include several interferon alpha formulations with FDA‑approved uses and selected off‑label uses, and interferon gamma (Actimmune) with distinct FDA indications. FDA‑approved indications for interferon alpha include treatment of genital warts (condylomata acuminata), Kaposi's sarcoma, chronic hepatitis B, hepatitis C, and malignant melanoma. Peginterferon alfa‑2b (Sylatron) is specifically addressed for adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection. Interferon gamma is covered only for its FDA‑approved indications: Chronic Granulomatous Disease and to delay progression in severe malignant osteopetrosis.

Revision History

2026-05removalLatest

Infergen (interferon Alfacon-1) removed from policy after being removed from market.

2026-03-15annual_review

Annual review completed (formatting changes only).

2023-07removal

OpenPayer

Interferons (alpha and gamma) — pharmacy policy