BlueCross BlueShield of Tennessee Medical Policy Manual

Ipilimumab (Yervoy®)

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the medical policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.

POLICY

          I.     INDICATIONS

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

A.    FDA-Approved Indications

1.     Unresectable or Metastatic Melanoma

Yervoy is indicated as a single agent or in combination with nivolumab for the treatment of unresectable or metastatic melanoma in adult and pediatric patients 12 years and older.

2.     Adjuvant Treatment of Melanoma

Yervoy is indicated for the adjuvant treatment of adult patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.

3.     Advanced Renal Cell Carcinoma

Yervoy, in combination with nivolumab, is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

4.     Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Metastatic Colorectal Cancer

Yervoy, in combination with nivolumab, is indicated for the treatment of adult and pediatric patients 12 years of age and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

5.     Hepatocellular Carcinoma

Yervoy, in combination with nivolumab, is indicated for the treatment of adult patients with hepatocellular carcinoma who have been previously treated with sorafenib.

6.     Metastatic Non-small Cell Lung Cancer

a.     Yervoy, in combination with nivolumab, is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

b.     Yervoy, in combination with nivolumab and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations.

7.     Malignant Pleural Mesothelioma

Yervoy, in combination with nivolumab, is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma.

8.     Esophageal Cancer

Yervoy, in combination with nivolumab, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

B.    Compendial Uses

1.     Cutaneous melanoma

2.     Uveal melanoma

3.     Central nervous system (CNS) brain metastases

4.     Non-small cell lung cancer

5.     Renal cell carcinoma

6.     Colorectal cancer, including appendiceal adenocarcinoma and anal adenocarcinoma

7.     Malignant pleural mesothelioma

8.     Malignant peritoneal mesothelioma

9.     Hepatocellular carcinoma

10.  Small bowel adenocarcinoma

11.  Ampullary adenocarcinoma

12.  Esophageal/Esophagogastric Junction Cancers

13.  Kaposi Sarcoma

14.  Bone Cancer

15.  Biliary Tract Cancers

a.     Cholangiocarcinoma

b.     Gallbladder Cancer

16.  Soft Tissue Sarcoma

a.     Extremity/body wall sarcoma

b.     Head/neck sarcoma

c.     Retroperitoneal/intra-abdominal sarcoma

d.     Rhabdomyosarcoma

e.     Angiosarcoma

17.  Merkel Cell Carcinoma

All other indications are considered experimental/investigational and not medically necessary.

         II.     DOCUMENTATION

Submission of the following information is necessary to initiate the prior authorization review:

A.    Documentation of laboratory report confirming MSI-H or mismatch repair deficient (dMMR) tumor status, where applicable.

B.    Documentation of molecular testing for EGFR exon 19 deletions or exon 21 L858R mutations and ALK rearrangements, where applicable

        III.    CRITERIA FOR INITIAL APPROVAL

A.    Cutaneous Melanoma

Authorization of 6 months may be granted for treatment of cutaneous melanoma in any of the following settings:

1.     The requested medication will be used as a single agent or in combination with nivolumab (for 4 doses followed by nivolumab as a single agent) for progressive, metastatic or unresectable disease.

2.     The requested medication will be used as a single agent or in combination with nivolumab as adjuvant treatment of stage III or IV disease if no evidence of disease following metastasis-directed therapy (i.e., complete resection).

3.     The requested medication will be used as subsequent therapy at a low dose in combination with pembrolizumab, or nivolumab for metastatic or unresectable disease in members who progressed on single-agent anti-programmed death 1 (PD-1) immunotherapy or BRAF-targeted therapy.

4.     The requested medication will be used as a single agent for limited resectable local recurrence after prior anti-PD-1 therapy.

B.    Uveal Melanoma

Authorization of 6 months may be granted as a single agent or in combination with nivolumab for treatment of uveal melanoma for distant metastatic disease.

C.    CNS Brain Metastases

Authorization of 6 months may be granted as a single agent or in combination with nivolumab for treatment of CNS brain metastases in members with melanoma.

D.    Non-Small Cell Lung Cancer (NSCLC)

Authorization of 6 months may be granted for treatment of recurrent, advanced or metastatic non-small cell lung cancer if there are no EGFR exon 19 deletions or exon 21 L858R mutations or ALK rearrangements (unless testing is not feasible due to insufficient tissue) and the requested medication will be used in a regimen containing nivolumab.

E.    Renal Cell Carcinoma 

Authorization of 6 months may be granted for treatment of renal cell carcinoma in combination with nivolumab (for 4doses, followed by single agent nivolumab) for relapsed, advanced, or stage IV disease with clear cell histology as:

1.     First-line therapy for poor or intermediate risk.

2.     First-line therapy for favorable risk.

3.     Subsequent therapy. 

F.    Colorectal Cancer

Authorization of 6 months may be granted for treatment of colorectal cancer, including appendiceal adenocarcinoma and anal adenocarcinoma, for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors when used in combination with nivolumab (for 4 doses followed by nivolumab as a single agent) for advanced, metastatic, unresectable, or inoperable disease.

G.    Malignant Pleural or Peritoneal Mesothelioma

Authorization of 6 months may be granted in combination with nivolumab for treatment of malignant pleural or peritoneal mesothelioma, including pericardial mesothelioma and tunica vaginalis testis mesothelioma.

H.    Hepatocellular Carcinoma

Authorization of 6 months may be granted as a single agent or in combination with nivolumab (for 4 doses followed by nivolumab as a single agent) for treatment of hepatocellular carcinoma.

I.      Small Bowel Adenocarcinoma

Authorization of 6 months may be granted in combination with nivolumab for treatment of advanced or metastatic small bowel adenocarcinoma for microsatellite-instability high (MSI-H) or mismatch repair deficient (dMMR) tumors.

J.     Ampullary Adenocarcinoma

Authorization of 6 months may be granted in combination with nivolumab for treatment of progressive, unresectable, or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) ampullary adenocarcinoma.

K.    Esophageal and Esophagogastric Junction Cancers

Authorization of 6 months may be granted in combination with nivolumab for the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC).

L.    Kaposi Sarcoma

Authorization of 6 months may be granted in combination with nivolumab for subsequent treatment of relapsed/refractory classic Kaposi Sarcoma.

M.   Bone Cancer

Authorization of 6 months may be granted in combination with nivolumab for unresectable or metastatic disease when all of the following are met:

1.   Disease has tumor mutation burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] tumors

2.   Disease has progressed following prior treatment and has no satisfactory alternative treatment options

N.    Biliary Tract Cancer (Cholangiocarcinoma and Gallbladder Cancer)

Authorization of 6 months may be granted as subsequent treatment in combination with nivolumab for unresectable or resected gross residual (R2) disease, progressive or metastatic disease that is tumor mutation burden-high (TMB-H).

O.    Soft Tissue Sarcoma

Authorization of 6 months may be granted in combination with nivolumab for treatment of extremity/body wall sarcomas, head/neck sarcomas and retroperitoneal/intra-abdominal sarcomas, rhabdomyosarcoma and angiosarcoma.

P.    Merkel Cell Carcinoma

Authorization of 6 months may be granted in combination with nivolumab for treatment of progressive, unresectable, recurrent, or stage IV Merkel cell carcinoma.

       IV.     CONTINUATION OF THERAPY

A.    Adjuvant Treatment of Melanoma

Authorization of 6 months may be granted (up to 3 years) for continued treatment in members requesting reauthorization for adjuvant melanoma when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

B.    Cutaneous Melanoma, Renal Cell Carcinoma, Colorectal Cancer, Hepatocellular Cancer

Authorization of 6 months may be granted (up to 4 doses maximum, if member has not already received 4 doses) for continued treatment in members requesting reauthorization for cutaneous melanoma, renal cell carcinoma, colorectal cancer, and hepatocellular cancer when treatment guidelines do not specify a limited number of total doses (see above) and there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

C.    Non-Small Cell Lung Cancer, Esophageal/Esophagogastric Junction Cancers, or Malignant Pleural Mesothelioma

Authorization of 6 months may be granted (up to 24 months total) for continued treatment in members requesting reauthorization for non-small cell lung cancer, esophageal cancer, or malignant pleural mesothelioma, including pericardial mesothelioma and tunica vaginalis testis mesothelioma subtypes, when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

D.    All Other Indications

Authorization of 6 months may be granted for continued treatment in members requesting reauthorization for all other indications listed in Section III when treatment guidelines do not specify a limited number of total doses (see above) and there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

MEDICATION QUANTITY LIMITS

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

ADDITIONAL INFORMATION  

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

REFERENCES

1.     The NCCN Drugs & Biologics Compendium 2023 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org. Accessed March 8, 2023.

2.     National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Anal Carcinoma. Version 3.2022. https://www.nccn.org/professionals/physician_gls/pdf/anal.pdf Accessed March 8, 2023.

3.     Lexicomp [database online]. Hudson, OH: Lexi-Comp, Inc.; https://online.lexi.com/lco/action/home [available with subscription]. Accessed March 13, 2023.

ORIGINAL EFFECTIVE DATE: 9/11/2011

MOST RECENT REVIEW DATE: 4/1/2024

ID_CHS

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

This document has been classified as public information.