Oncologic uses of Interferon Therapy - CAM 80103

Interferon comprises approximately 20 naturally occurring proteins. Three classes of interferons have been identified: alpha, beta and gamma. Each class is chemically unique, is synthesized and released primarily by different sets of cells and has a specific function.

Interferons play an important role in the immune system. Animal studies and preclinical human tissue studies suggest interferons have antiviral, antiproliferative, antiangiogenic, immunomodulatory and gene regulatory effects. There are two rationales for the use of interferons in clinical oncology. First, evidence suggests that interferons have a direct antiproliferative effect on some cancer cells by increasing the length of the cell cycle by depleting essential intracellular metabolites and by enhancing cell lysis. Second, interferon may have indirect effects, such as enhancement of cell-surface antigen expression, enhancement of macrophage and lymphocyte cytotoxicity and induction of antibodies to tumor cells.

The use of recombinant or natural interferon alfa for the treatment of hematologic malignancies (lymphomas, leukemias or plasma-cell malignancies) is MEDICALLY NECESSARY in off-label use for:

  • First-line treatment of patients with Philadelphia chromosome-positive CML in first chronic phase
  • As a component of first-line treatment of patients with multiple myeloma, or as maintenance therapy of patients with multiple myeloma that has responded to first-line therapy
  • A combination with cytotoxic agents as first-line therapy of aggressive low-grade (follicular) or intermediate-grade non-Hodgkin’s lymphoma
  • Carcinoid syndrome

INVESTIGATIONAL uses are as follows:

  • Recombinant or natural interferon alfa for the treatment of any off-label hematologic malignancy other than those specified above.
  • Recombinant interferon beta for the treatment of any hematologic malignancy.
  • Recombinant interferon gamma for the treatment of any hematologic malignancy.
  • Recombinant and human leukocyte-derived interferons are considered INVESTIGATIONAL for the treatment of any off-label solid tumor indications, including, but not limited to:
    • Bladder cancer
    • Brain tumors, malignant
    • Breast cancer
    • Cancer or precancers of oral cavity
    • Cervical intraepithelial neoplasia II associated with human papillomavirus infection
    • Colorectal cancer
    • Cutaneous squamous cell cancer (including actinic keratoses, basal cell carcinomas)
    • Head and neck cancers, recurrent or metastatic
    • Lung cancer, nonsmall-cell
    • Malignant islet-cell tumors
    • Medullary thyroid carcinoma
    • Melanoma
    • Merkel cell carcinoma
    • Metastatic apudomas
    • Neuroendocrine tumors
    • Osteosarcoma
    • Ovarian cancer
    • Pancreatic cancer
    • Recurrent respiratory papillomatosis
    • Relapsed adult nephroblastoma
    • Renal cell carcinoma
    • Teratoma, testicular, mature-growing 


  1. Goodin DS, Frohman EM, Hurwitz B, et al. Neutralizing antibodies to interferon beta: Assessment of their clinical and radiographic impact: An evidence report: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2007;68(13):977-984.
  2. Brady B, Siebert U, Sroczynski G, et al. Clinical and cost-effectiveness of interferon-based therapies for chronic hepatitis C virus infection. Technology Overview No. 27. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health (CADTH); 2007.
  3. Brady B, Siebert U, Sroczynski G, et al. Pegylated interferon combined with ribavirin for chronic hepatitis C virus infection: An economic evaluation. Technology Report No. 82. Ottawa, ON: CADTH; 2007.
  4. Hodson EM, Jones CA, Strippoli GFM, et al. Immunoglobulins, vaccines or interferon for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2007.
  5. National Comprehensive Cancer Network (NCCN). Hepatobiliary cancers. NCCN Clinical Practice Guidelines in Oncology. v.2.2008. Fort Washington, PA: NCCN; 2008.
  6. National Comprehensive Cancer Network (NCCN). Soft tissue sarcoma. NCCN Clinical Practice Guidelines in Oncology. v.1.2008. Fort Washington,  PA; NCCN; 2008.
  7. National Comprehensive Cancer Network (NCCN). Non-Hodgkin lymphomas. NCCN Clinical Practice Guidelines in Oncology. v.3.2008. Fort Washington, PA: NCCN; 2008.
  8. Clerico M, Faggiano F, Palace J, et al. Recombinant interferon beta or glatiramer acetate for delaying conversion of the first demyelinating event to multiple sclerosis. Cochrane Database Syst Rev. 2008;(2):CD005278
  9. Bacon BR, Shiffman ML, Mendes F, et al. Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results. Hepatology. 2009;49(6):1838-1846.
  10. Trepo C, Pradat P. Hepatitis C: CIFN for re-treatment of PEG-IFN plus RBV nonresponders? Nat Rev Gastroenterol Hepatol. 2009;6(10):570-571.
  11. Lo GH. Re-treating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: Really safe and effective? Hepatology. 2009;50(3):988-989.
  12. Whelan J, Patterson D, Perisoglou M, et al. The role of interferons in the treatment of osteosarcoma. Pediatr Blood Cancer. 2010;54(3):350-354.
  13. Hughes RA, Gorson KC, Cros D, et al. Intramuscular interferon beta-1a in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology. 2010;74(8):651-657.

Coding Section

Codes Number Description
CPT 96365 Intravenous infusion, for therapy, prophylaxis or diagnosis (specify substance or drug); initial, up to 1 hour
  96366 each additional hour, up to 8 hours (list separately in addition to code for primary procedure)
  96372 Therapeutic, prophylactic or diagnostic injection (specify substance or drug); subcutaneous or intramuscular
ICD-9 Procedure 99.28

Injection or infusion of biological response

ICD-9 Diagnosis 202.80-202.88 Other lymphomas

Multiple myeloma

  205.10-205.13 Chronic myelogenous leukemia code range

Interferon beta-1lb, per 0.25 mg


Injection, interferon alfa-2a, recombinant, 3 million units

  J9214 Injection, interferon alfa-2b, recombinant, 1 million units
  J9215 Injection, interferon, alfa-n3, (human leukocyte derived), 250,000 IU
  J9216 Injection, interferon, gamma-1b, 3 million units
ICD-10-CM (effective 10/01/15) C85.10-C85.99

Other and unspecified types of non-Hodgkin lymphoma; code range

  C90.00-C90.02 Multiple myeloma; code range
  C92.10-C92.12 Chronic myeloid leukemia, BCR/ABL positive; code range
ICD-10-PCS (effective 10/01/15)   ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for this procedure
  3E01305 Administration, introduction, percutaneous, subcutaneous tissue, antineoplastic, other

Administration, introduction, percutaneous, muscle, antineoplastic, other

  3E03305 Administration, introduction, percutaneous, peripheral vein, antineoplastic, other
  3E04305 Administration, introduction, percutaneous, central vein, antineoplastic, other
Type of Service Therapy  
Place of Service Inpatient/Outpatien/Home  

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines. 

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2013 Forward     


Annual review, no change to policy intent. 


Annual review, no change to policy intent. 


Annual review, no change to policy intent. 


Annual review, no change to policy intent.


Annual review, no change to policy intent. 


Annual review, no change to policy intent. 


Annual review, no change to policy intent. 


Added coding to policy.  


Annual review. Updated title to indicate this is for Oncologic uses of Interferon. Removed carcinoid syndrome from investigational and moved it to potentially medically necessary use of this drug. No other changes. 


Annual Review. No changes.  


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