ARCHIVED

Medical Policy

Policy Num:      08.001.013
Policy Name:    Interferon Therapy
Policy ID:          [08.001.013]  [Ar / B / M+ / P]  [8.01.03]

Last Review:       June 06, 2022
Next Review:       Policy Archived
Issue:                   6:2022

ARCHIVED

Related Policies: None

 Interferon Therapy

Summary

Interferon is one of about 20 naturally occurring proteins. Three classes of interferons have been identified; alpha, beta and gamma. Each of these classes is chemically unique, distinct, synthesized and released by different groups of cells. Each one has a specific function. 

Interferons play a very important part in the immune system. Animal and preclinical studies in human tissues suggest that interferons have antiviral, antiproliferative, antiangiogenic, immunomodulatory, and gene regulatory properties. Its application in clinical oncology is based on the following observations:

 • Evidence suggests that interferons have a direct antiproliferative effect on some cancer cells.

• Increase cycle length and deplete essential intracellular metabolites, promoting cell lysis or destruction.

• The proposed mechanism of action is the activation of the expression of surface antigens.

• Macrophage activity, lymphocyte cytotoxicity, and induction of antibodies to tumor cells are enhanced.

Objective

The objective is to review the accepted and the off label uses of interferon.

Policy Statements

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.

Policy Guidelines

The FDA has approved 5 forms of interferons (IFNs) for clinical use: IFNα-2a (Roferon-A), IFNα-2b (Intron-A), IFNα-n3 (Alferon N), IFNß-1b (Betaseron), IFN -y, (Actimune).

 The use of natural or recombinant interferon in hematological malignancies (lymphomas, leukemias, plasma cell cancer) is considered for payment under the following conditions:

• Hairy cell leukemia

• Kaposi's Sarcoma of AIDS

• Condyloma acuminata

• Chronic Hepatitis B

• Chronic Hepatitis C

• Recurrent malignant melanoma

• Multiple sclerosis

In the following indications "off label" are considered for payment:

• First-line treatment for Philadelphia chromosome-positive CML patients in their first chronic phase.

• First-line or maintenance treatment for patients with multiple myeloma who have responded to first interferon therapy.

• In combination with other cytotoxic agents as first line therapy for Non-Hodgkin's Lymphoma (low, intermediate grade).

The use of interferon is not considered for payment under the following conditions:

• Other hematological malignancies not indicated in the coverage policy.

• Solid tumors, including but not limited to the following:

o bladder cancer

o breast cancer

o Cancer or pre-cancer of the oral cavity

o Carcinoid tumors or carcinoid syndromes

o Malignant brain tumors

o Cervical Intraepithelial Neoplasia II associated with human papillomavirus

o colorectal cancer

o Spinocellular skin cancer (including actinic keratosis, basal cell carcinoma

o Head and neck cancer

o lung cancer

o Pancreatic cancer (islet-cell)

o Medullary carcinoma of the thyroid

o Early Melanoma

o Merkel's carcinoma

o Metastatic apudomas of neuroendocrine tumors

o osteosarcoma

o ovarian cancer

o Recurrent respiratory papillomatosis

o Recurrent adult nephroblastoma

o Kidney carcinoma (renal cell)

o testicular teratoma

Benefit Application

BlueCard/National Account Issues

See Off-Label Use of Drugs, Policy No. 8.01.03, under the Prescription Drug section of this manual.

Background

Interferons are categorized as cytokines, small proteins that are involved in intercellular  signaling. Interferon is secreted  by cells in resonse to stimulation by a virus or other foreign substance , but it does not directly inhibit the virus multiplication. It rather sitmulates the infected cells and those nearby to produce proteins that prevent the virus from replicating within them. Further production of the virus is thereby inhibited and the infection stemmed. Interferons have immonoregulatory functions, they inhibit B-lymphocytes (B-cell) activation, enhance T lymphocytes (T-cells) activity and increase the cellular-destructuon capability of natural killer cells.

Regulatory Status

N/A

Rationale

Population Reference No. 1 

Individuals: Condyloma acuminate, Interventions of interest are: interferon therapy, Comparators of interest are: no treatment, another therapy.

Population Reference No. 2

Individuals: Malignant melanoma, Interventions of interest are: interferon therapy, Comparators of interest are: no treatment, another therapy, Relevant outcomes include: functional outcome, quality of life, treatment morbidity.

Population Reference No. 3

Individuals: Chronic hepatitis B, chronic hepatitis C, Interventions of interest are: interferon therapy, Comparators of interest are: no treatment, another therapy, Relevant outcomes include: functional outcome, quality of life, treatment morbidity.

Population Reference No. 4 

Individuals: Kaposi’s sarcoma, Interventions of interest are: interferon therapy, Comparators of interest are: no treatment, another therapy, Relevant outcomes include: functional outcome, quality of life, treatment morbidity.

Population Reference No. 5

Individuals: Non-Hodgkin lymphoma; code range, Interventions of interest are: interferon therapy, Comparators of interest are: no treatment, another therapy, Relevant outcomes include: functional outcome, quality of life, treatment morbidity.

Population Reference No. 6 

Individuals: Multiple myeloma: code range, Interventions of interest are: interferon therapy, Comparators of interest are: no treatment, another therapy, Relevant outcomes include: functional outcome, quality of life, treatment morbidity.

Population Reference No. 7

Individuals: Hairy cell leukemia, Interventions of interest are: interferon therapy, Comparators of interest are: no treatment, another therapy, Relevant outcomes include: functional outcome, quality of life, treatment morbidity.

Population Reference No. 8

Individuals: Chronic myeloid leukemia, BCR/ABL positive; code range, Interventions of interest are: interferon therapy, Comparators of interest are: no treatment, another therapy, Relevant outcomes include: functional outcome, quality of life, treatment morbidity.

Population Reference No. 9

Individuals: Multiple sclerosis, Interventions of interest are: interferon therapy, Comparators of interest are: no treatment, another therapy, Relevant outcomes include: functional outcome, quality of life, treatment morbidity.

Population Reference No. 10

Individuals: Solid tumors of: Breast, Brain, Cervix, Lung, Pancreas, Thyroid, Neuroendocrine, Kidney, Testicular, Colorectal, Interventions of interest are: interferon therapy, Comparators of interest are: no treatment, another therapy, Relevant outcomes include: functional outcome, quality of life, treatment morbidity.

Supplemental Information

N/A

Practice Guidelines and Position Statements

N/A

Medicare National Coverage

N/A

References

A search of the literature was completed through the MEDLINE database for the period of January 1985 through May 1995. The search strategy focused on references containing the following Medical Subject Headings:

• Interferon Linked with Drug Therapy in Conjunction with Neoplasm
• Lymphoma, Leukemia, Multiple Myeloma Combined with Random Allocation or “Randomized Controls Trials”

 Research was limited to English-language journals on humans.

 See also:

Current Contents

Abstracts from the following groups:

• American Society for Clinical Oncology
• American Society for Therapeutic and Radiation Oncology
• American Society for Hematology
• Keystone Symposia on Bone Marrow Transplantation
• The American Society for Blood and Marrow Transplantation
• The International Symposia on Bone Marrow Transplantation

TEC Assessments 1995:

Off-Label Oncology indications - Lymphomas, Leukemias, and Plasma-Cell Malignancies -

Tab 16.

Off-Label Oncology Indications - Solid Tumor - Tab 17

1.    Betaseron (interferon beta-1b) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; January 2014.

2.    Betaseron (interferon beta-1b) [product monograph]. Toronto, Ontario, Canada: Bayer Inc; November 2012

Codes

Appplicable Modifiers

N/A

Policy History