Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Ipilimumab (Yervoy®)
Policy #:MA08.059f

This policy is applicable to the Company’s Medicare Advantage products only. Policies that are applicable to the Company’s commercial products are accessible via a separate commercial policy database.


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.


This Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

Ipilimumab (Yervoy®) is considered medically necessary and, therefore, covered when the Dosing and Frequency Requirements listed in Attachment A and the following indications are met:

CENTRAL NERVOUS SYSTEM CANCERS: BRAIN METASTASES
For the treatment of brain metastases in individuals with melanoma, as single-agent therapy or in combination with nivolumab (Opdivo®) in one of the following scenarios, if active against the primary tumor (melanoma).
  • Limited metastatic brain lesions* (e.g., small asymptomatic brain metastases)
    • Newly diagnosed and stable systemic disease or having reasonable systemic treatment options, in combination with nivolumab (Opdivo®)
    • Recurrent metastatic brain lesions, as a single agent or in combination with nivolumab (Opdivo®)
  • Extensive metastatic brain lesions**
    • Recurrent metastatic brain lesions, and stable systemic disease or having reasonable systemic treatment options, as a single agent or in combination with nivolumab (Opdivo®).

*Limited brain metastases defines a group of individuals for whom sterotactic radiosurgery is equally effective and offers significant cognitive protection compared with whole brain radiation therapy. The definition of limited brain metastases in terms of number of metastases or total intracranial disease volume is evolving and may depend on the specific clinical situation.

**Extensive brain metastases is defined as all cases that do not fit the definition of "limited brain metastases."


CUTANEOUS MELANOMA (METASTATIC OR UNRESECTABLE)
For individuals ages 12 years and older, with metastatic or unresectable disease, that occurs in one of the following scenarios:

  • First-line therapy in combination with nivolumab (Opdivo®) as an National Comprehensive Cancer Network (NCCN)-preferred regimen*
  • Second-line or subsequent therapy after disease progression or maximum clinical benefit from BRAF targeted therapy for any of the following scenarios:
    • Single agent if anti-PD-1 therapy was not previously used
    • In combination with nivolumab (Opdivo®) as an NCCN-preferred regimen* or as a single agent if anti-PD-1 therapy was not previously used or for disease progression on single agent anti-PD-1 therapy
    • Re-induction therapy as a single agent or in combination with nivolumab, if prior checkpoint inhibitor immunotherapy resulted in disease control (complete response, partial response, or stable disease) and no residual toxicity, and disease progression/relapse occurred greater than three months after treatment discontinuation.

*In accordance with National Comprehensive Cancer Network (NCCN), preferred regimens include interventions that are based on superior efficacy, safety and evidence.

CUTANEOUS MELANOMA (ADJUVANT TREATMENT AFTER COMPLETE RESECTION)
As a high-dose single agent, for adjuvant treatment in individuals with cutaneous melanoma with pathologic involvement of regional lymph nodes and a documented failure, contraindication, or intolerance to nivolumab (Opdivo®) or pembrolizumab (KEYTRUDA®), in one of the following scenarios:
  • Stage IIIA disease with sentinel lymph node positive metastasis > 1 mm , stage IIIB or stage IIIC disease (but with no in-transit metastases) following complete lymph node dissection (CLND) including total lymphadenectomy
  • Nodal recurrence, following CLND and/ or complete resection of nodal metastasis
  • Stage IV disease, following complete resection of stage IV disease

UVEAL MELANOMA
For individuals with uveal melanoma, distant metastatic or unresectable disease, as single-agent therapy or in combination with nivolumab (Opdivo®).

MALIGNANT PLEURAL MESOTHELIOMA
For individuals with malignant pleural mesothelioma, as a subsequent systemic therapy in combination with nivolumab (Opdivo®)

COLORECTAL CANCER
For individuals ages 12 years and older, with colorectal cancer, metastatic disease in combination with nivolumab (Opdivo®) that occurs in either of the following scenarios:
  • Primary treatment for unresectable metachronous metastases (dMMR or MSI-H only) and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months
  • Subsequent therapy (if no previous treatment with anti-PD-1 therapy), for unresectable advanced or metastatic disease (dMMR or MSI-H only) following previous oxaliplatin- irinotecan- and/or fluoropyrimidine-based therapy
SMALL BOWEL ADENOCARCINOMA
For individuals with small bowel adenocarcinoma in combination with nivolumab (Opdivo®) that occurs in either of the following scenarios:
  • Initial therapy for advanced or metastatic disease (dMMR or MSI-H] only) and prior oxaliplatin exposure in the adjuvant setting or contraindication to oxaliplatin.
  • Subsequent therapy for advanced or metastatic disease (dMMR or MSI-H only)

RENAL CELL CARCINOMA (RCC)
For individuals with relapse or stage IV disease in combination with nivolumab (Opdivo®) that occurs in one of the following scenarios:
  • First-line therapy for clear cell histology and favorable risk
  • First-line therapy for clear cell histology and poor/intermediate risk as an NCCN-preferred regimen
  • Subsequent therapy for clear cell histology as an NCCN-preferred regimen

NON-SMALL CELL LUNG CANCER (NSCLC)
For individuals with non-small cell lung cancer (NSCLC) in combination with nivolumab (Opdivo®) as first-line therapy when both of the following criteria are met:
  • Cytologically confirmed stage IV disease or recurrent NSCLC
  • Activity against tumor mutational burden (TMB)*, (greater than or equal to 10 mutations per megabase)

*Tumor mutational burden is a measurement of mutations carried by tumor cells and is a predictive biomarker being studied to evaluate its association with response to Immuno-Oncology therapy


SMALL CELL LUNG CANCER (SCLC)
For individuals with small cell lung cancer (SCLC), in combination with nivolumab (Opdivo®) as a subsequent systemic therapy that occurs in either of the following scenarios:

  • Primary progressive SCLC
  • Relapse SCLC within six months following complete or partial response or stable disease with initial treatment (not recommended for relapse disease in individuals on maintenance atezolizumab (TECENTRIQ®) at time of relapse)

EXPERIMENTAL/INVESTIGATIONAL

All other uses of ipilimumab (Yervoy®) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

DOSING AND FREQUENCY REQUIREMENTS

Refer to Attachment A for the Dosing and Frequency Requirements for ipilimumab (Yervoy®).

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this policy to ensure consistency with the most recently published recommendations for the use of ipilimumab (Yervoy®). Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of ipilimumab (Yervoy®) outside of the Dosing and Frequency Requirements listed in this policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of (for single drugs in a policy, state “this drug”) these drugs. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for ipilimumab (Yervoy®).

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the drug. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial of the drug.

When coverage of ipilimumab (Yervoy®) is requested outside of the Dosing and Frequency Requirements listed in this policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.
Policy Guidelines

There is no Medicare coverage determination addressing this service; therefore, the Company policy is applicable.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, ipilimumab (Yervoy®) is covered under the medical benefits of the Company's Medicare Advantage products when the medical necessity criteria and Dosing and Frequency Requirements listed in this medical policy are met.

Certain drugs are available through either the member's medical benefit (Part B) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when ipilimumab (Yervoy®) is covered under a member's medical benefit (Part B benefit). It does not address instances when ipilimumab (Yervoy®) is covered under a member's pharmacy benefit (Part D benefit).

BLACK BOX WARNING

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Ipilimumab (Yervoy®) was approved by the FDA on March 25, 2011 for the treatment of unresectable or late-stage metastatic melanoma. Supplemental approvals for have since been issued by the FDA.

PEDIATRIC USE

The safety and effectiveness of ipilimumab (Yervoy®) have not been established in pediatric individuals.

Description

Ipilimumab (Yervoy®), an intravenously delivered agent, is a recombinant human IgG1 immunoglobulin monoclonal antibody that binds to the cytotoxic T-lymphocyte associated antigen 4 (CTLA-4). CTLA-4 is a down-regulator of T-cell activation pathways. Blocking CTLA-4 allows for enhanced T-cell activation and proliferation. Ipilimumab (Yervoy®) is indicated for use in individuals with malignant melanoma, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer, and renal cell carcinoma.


PEER-REVIEWED LITERATURE

SUMMARY
Unresectable or Metastatic Melanoma, as a Single Agent

The FDA granted approval of ipilimumab (Yervoy®) based on a double-blind, Phase III study of 676 individuals who had been previously treated with other chemotherapeutic agents and had a diagnosis of unresectable or metastatic melanoma. Ninety-eight percent of these individuals also had Eastern Cooperative Oncology Group (ECOG) performance status scores of 0 and 1. As part of the study, individuals received ipilimumab (Yervoy®) 3 mg/kg as an intravenous infusion administered over 90 minutes every three weeks for a total of four doses. The overall survival rate of the participants significantly improved compared to other therapeutic agents.

Unresectable or Metastatic Melanoma, in Combination with Nivolumab (Opdivo®)

The combined use of ipilimumab (Yervoy®) and nivolumab (Opdivo®) was FDA approved based on a Phase III, randomized (1:1:1), double-blind, multicenter, study of 945 individuals with untreated unresectable or metastatic melanoma. The three arms of the study consisted of:

    1. Nivolumab (Opdivo®) 1 mg/kg with ipilimumab (Yervoy®) 3 mg/kg every 3 weeks for 4 doses, followed by nivolumab (Opdivo®) 3 mg/kg as a single agent every 2 weeks (Combination arm),
    2. Nivolumab (Opdivo®) 3 mg/kg every 2 weeks (nivolumab [Opdivo®] arm)
    3. Ipilimumab (Yervoy®) 3 mg/kg every 3 weeks for 4 doses followed by placebo every 2 weeks (ipilimumab [Yervoy®] arm).

Progression-free survival (PFS) was defined as the time between the date of randomization and the date of documented progression or death, whichever occurred first. PFS in the combination arm was 11.5 months, as compared with 6.9 months in the nivolumab (Opdivo®) arm and 2.9 months in the ipilimumab (Yervoy®) arm. PFS was statistically significantly longer in the Combination arm than in the ipilimumab (Yervoy®) arm. PFS was also statistically significantly longer in the nivolumab (Opdivo®) arm than in the ipilimumab (Yervoy®) arm.

Adjuvant Treatment of Individuals with Cutaneous Melanoma

The safety and efficacy of ipilimumab (Yervoy®) was studied for the adjuvant treatment of melanoma through a randomized (1:1), double-blind, placebo-controlled trial in 951 individuals with resected Stage IIIA (>1 mm nodal involvement), IIIB, and IIIC (with no in-transit metastases) histologically confirmed cutaneous melanoma. Individuals received ipilimumab (Yervoy®) 10 mg/kg or placebo as an intravenous infusion every 3 weeks for 4 doses, followed by ipilimumab (Yervoy®) 10 mg/kg or placebo every 12 weeks from Week 24 to Week 156 (3 years) or until documented disease recurrence or unacceptable toxicity. One primary efficacy outcome was recurrence-free survival (RFS) defined as the time between the date of randomization and the date of first recurrence (local, regional, or distant metastasis) or death, whichever occurs first. RFS was significantly improved in those to received ipilimumab (Yervoy®) (49% at a median of 26 months) compared to those who received placebo (62% at a median of 17 months). Another primary efficacy outcome was overall survival; final analysis is still pending for this study.

The efficacy of nivolumab (Opdivo®) versus ipilimumab (Yervoy®) for adjuvant therapy in individuals with resected advanced melanoma was studied in a randomized, double-blind, phase 3 trial. 906 individuals who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma were randomized to receive an intravenous infusion of either nivolumab (Opdivo®) 3 mg/kg every 2 weeks or ipilimumab (Yervoy®) 10 mg/kg every 3 weeks for four doses and then every 12 weeks. Individuals were treated for up to 1 year or until disease recurrence, a report of unacceptable toxicity, or withdrawal of consent. The primary endpoint was recurrence-free survival in the intention to treat population. At a minimum follow up of 18 months, the 12 month rate of recurrence free survival was 70.5% in the nivolumab (Opdivo®) group versus 60.8% in the ipilimumab (Yervoy®) group. Treatment related grade 3 or 4 adverse events were reported in 14.4% of the individuals in the nivolumab (Opdivo®) group versus 45.9% in the ipilimumab (Yervoy®) group. Treatment was discontinued in 9.7% of nivolumab (Opdivo®) treated individuals and 42.6% of ipilimumab (Yervoy®) treated individuals due to adverse effects, and 2 deaths related to toxicity were reported in the ipilimumab (Yervoy®) group more than 100 days after treatment. These results indicated that therapy with nivolumab (Opdivo®) had significantly longer recurrence free survival with a lower rate of grade 3 or 4 adverse events that adjuvant therapy with ipilimumab (Yervoy®).

Advanced Renal Cell Carcinoma (RCC)

The efficacy of ipilimumab (Yervoy®) was studied in a randomized (1:1), open-label trial in intermediate/poor risk individuals with previously untreated advanced RCC who had at least 1 or more of 6 prognostic risk factors as per the IMDC criteria (less than one year from time of initial renal cell carcinoma diagnosis to randomization, Karnofsky performance status <80%, hemoglobin less than the lower limit of normal, corrected calcium of greater than 10 mg/dL, platelet count greater than the upper limit of normal, and absolute neutrophil count greater than the upper limit of normal).
The two arms of the study were:
  • nivolumab (Opdivo®) 3 mg/kg plus ipilimumab (Yervoy®) 1 mg/kg (n=425) IV every 3 weeks for 4 doses followed by nivolumab (Opdivo®) monotherapy 3 mg/kg every two weeks until disease progression or unacceptable toxicity.
  • sunitinib (n=422) 50 mg orally daily for 4 weeks followed by 2 weeks off, every cycle. Treatment continued until disease progression or unacceptable toxicity.

The primary efficacy outcomes were OS, PFS, and confirmed ORR. The results of this trial demonstrated statistically significant improvement in median OS (not estimated vs. 25.9 months) and ORR (41.6% vs. 26.5%) for individuals randomized to nivolumab (Opdivo®) plus ipilimumab (Yervoy®) as compared with sunitinib. Furthermore, the OS benefit was observed regardless of PD-L1 expression level. However, this trial did not demonstrate a statistically significant improvement in median PFS (11.6 months vs. 8.4 months) for individuals randomized to nivolumab (Opdivo®) plus ipilimumab (Yervoy®) as compared with sunitinib.

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

On July 10, 2018, the FDA granted accelerated approval to ipilimumab (Yervoy®), in combination with nivolumab, indicated for the treatment of adult and pediatric individuals 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.

The approval was based on data from CHECKMATE-142 a multicenter, non-randomized, multiple parallel-cohort, open-label study that enrolled 82 individuals. Key eligibility criteria were at least one prior line of treatment for metastatic disease, ECOG PS 0 or 1, and absence of the following: active brain metastases, active autoimmune disease, or medical conditions requiring systemic immunosuppression. All study participants received ipilimumab 1 mg/kg by intravenous (IV) infusion and nivolumab 3 mg/kg IV every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg IV as a single agent every 2 weeks, until unacceptable toxicity or radiographic progression.

Among these 82 enrolled individuals, the overall response rate as assessed by an independent radiographic review committee using Response Evaluation Criteria in Solid Tumors (RECIST) Guideline version 1.1, was 46 percent (95 percent CI: 35,58), with 3 complete and 35 partial responses, and 89 percent of responding individuals had response durations of six months or greater. The overall response rate was higher than that observed in a separate cohort of 58 individuals with dMMR/MSI-H mCRC with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy who received nivolumab alone, with an ORR of 28 percent with 67 percent having response durations of six months or greater.


OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.


References

Carvajal RD, Hamid O, Ariyan C. Mucosal melanoma. Up to Date.[UpToDate Web Site]. 11/07/2018. Available at: http://www.uptodate.com/contents/mucosal-melanoma?source=search_result&search=mucosal+melanoma&selectedTitle=1%7E10 [via subscription only]. Accessed March 08, 2019.

Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus Ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093-2104.


Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-723.

Ipilimumab (Yervoy). American Hospital Formulary Service (AHFS). Drug Information 2019. [Lexicomp Online Web Site]. 02/22/2019. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/complete_ashp/3596963 [via subscription only]. Accessed March 08, 2019.

Ipilimumab (Yervoy). Elsevier’s Clinical Pharmacology Compendium.[Clinical Pharmacology Web site]. 03/22/2019. Available at: https://www.clinicalkey.com/pharmacology/monograph/3721?sec=monindi&n=YERVOY [via subscription only]. Accessed March 08, 2019.

Ipilimumab (Yervoy). Micromedex® Healthcare Series. DrugDex®.[Micromedex® Web site]. 03/25/2019. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 08, 2019.

Ipilimumab (Yervoy). Package Insert. Bristol-Myers Squibb; Princeton, NJ. Updated June 2018. Available at: http://www.yervoy.com/ . Accessed March 08, 2019.

Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(1):23-34.

Lexi-Drugs Compendium. Ipilimumab (Yervoy). [Lexicomp Online Web site]. 04/01/2019. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/2934459 [via subscription only]. Accessed March 08, 2019.

Lexi-Drugs Compendium. Nivolumab (Opdivo). [Lexicomp Online Web site]. 04/02/2019. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/5467454 [via subscription only]. Accessed March 08, 2019.

Margolin K, Ernstoff MS, Hamid O, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13(5):459-65.
National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 1.2019; CNS Cancers. [NCCN Website]. 03/05/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. [via free subscription only]. Accessed March 08, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 1.2019; Melanoma. [NCCN Website]. 03/12/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf [via subscription only]. Accessed March 08, 2019.

National Comprehensive Cancer Network (NCCN). Drugs and Biologics Compendium. Ipilimumab. [NCCN Website]. 2019. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed March 08, 2019.

National Comprehensive Cancer Network (NCCN). Drugs and Biologics Compendium. Nivolumab. [NCCN Website]. 2019. Available at:
http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed March 08, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology- Kidney Cancer. V.3.2019. [NCCN Web site]. 02/06/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf [via subscription only]. Accessed March 08, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology-Malignant Pleural Mesothelioma .V2.2019. [NCCN Web site]. 04/01/2019. Available at:
https://www.nccn.org/professionals/physician_gls/pdf/mpm.pdf. Accessed November 19, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology- Small Cell Lung Cancer.V1.2019. [NCCN Web site]. 10/10/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf [via subscription only]. Accessed March 08, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology- Colon Cancer. V4.2018. [NCCN Web site]. 10/19/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf [via subscription only]. Accessed March 08, 2019.
National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology-Rectal Cancer. V3.2018. [NCCN Web site]. 08/07/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf [via subscription only]. Accessed March 08, 2019.
National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology-Uveal Melanoma. V1.2019. [NCCN Web site]. 06/14/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uveal.pdf. Accessed March 08, 2019.

National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology- Small Bowel Adenocarcinoma. V1.2020. [NCCN Web Site]. 07/30/2019. Available at:https://www.nccn.org/professionals/physician_gls/pdf/small_bowel.pdf. Accessed July 30, 2019.

Nivolumab (Opdivo). American Hospital Formulary Service (AHFS). Drug Information 2019. [Lexicomp Online Web Site]. 02/22/2019. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/complete_ashp/5756161 [via subscription only]. Accessed March 08, 2019.

Nivolumab (Opdivo). Elsevier’s Clinical Pharmacology Compendium.[Clinical Pharmacology Web site]. 03/22/2019. Available at: https://www.clinicalkey.com/pharmacology/monograph/3973?sec=monindi&n=Opdivo. [via subscription only]. Accessed March 08, 2019.

Nivolumab (Opdivo). Micromedex® Healthcare Series. DrugDex®.[Micromedex® Web site]. 02/15/2019. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 08, 2019.

Nivolumab (Opdivo) Package Insert. Bristol-Myers Squibb; Princeton, NJ. Updated March 2019. Available at: http://packageinserts.bms.com/pi/pi_opdivo.pdf . Accessed March 08, 2019.

Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

Overman MJ, Lonardi S, Wong KYM, et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36(8):773-779.

Piulats JM, Cruz-Merino LDL, Garcia MTC, et al. Phase II multicenter, single arm, open label study of nivolumab (NIVO) in combination with ipilimumab (IPI) as first line in adult patients (pts) with metastatic uveal melanoma (MUM): GEM1402 NCT02626962. J Clin Oncol. 2017;35:Abstr 9533.


Postow MA, Hamid O, Carvajal RD. Mucosal melanoma: pathogenesis, clinical behavior, and management. Curr Oncol Rep. 2012;14(5):441-8.

Scherpereel A, Mazieres J, Greillier L, et al. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial. Lancet Oncol. 2019;20(2):239-253.

Tanabe KK, Tyler D. Cutaneous melanoma: In transit metastases. [UpToDate Web Site]. Updated: 05/08/2018. Available at: http://www.uptodate.com/contents/cutaneous-melanoma-management-of-in-transit-metastase[via subscription only]. Accessed March 08, 2019.

US Food and Drug Administration (FDA). Ipilimumab (Yervoy) Prescribing Information. [FDA Web site]. 09/20/2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125377s104lbl.pdf . Accessed September 20, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Nivolumab (Opdivo) Approval letter and Prescribing Information. [FDA Website]. 09/20/2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125377s104lbl.pdf Accessed September 20, 2019.



Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See Attachment B


HCPCS Level II Code Number(s)

J9228 Injection, ipilimumab, 1 mg


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Ipilimumab (Yervoy®)
Description: Dosing and Frequency Requirements For Ipilimumab (Yervoy®)

Attachment B: Ipilimumab (Yervoy®)
Description: ICD-10 Diagnosis codes






Policy History

Revisions from MA08.059f
12/30/2019This version of the policy will become effective 12/38/2019.

This policy has been updated in consideration of revisions within the US Food and Drug Administration (FDA) labeling; the National Comprehensive Cancer Network (NCCN) Compendia and Clinical Practice Guidelines in Oncology.

Coverage was added for the conditions of uveal melanoma, malignant pleural mesothelioma, colorectal cancer, small bowel adenocarcinoma, and non-small cell lung cancer, with criteria.

The following ICD-10 CM codes have been added to this policy:

C17.0, C17.1, C17.2, C17.3, C17.8, C17.9, C18.0, C18.1, C18.2, C18.3, C18.4, C18.5, C18.6, C18.7, C18.8, C18.9, C20, C45.0

Revisions from MA08.059e
10/01/2018This policy has been identified for the ICD-10 CM code update, effective 10/01/2018.

The following CD-10 CM codes have been termed from this policy:
C43.11 Malignant melanoma of right eyelid, including canthus

C43.12 Malignant melanoma of left eyelid, including canthus


The following ICD-10 CM codes have been added to the Attachment B:
C43.111 Malignant melanoma of right upper eyelid, including canthus

C43.112 Malignant melanoma of right lower eyelid, including canthus

C43.121 Malignant melanoma of left upper eyelid, including canthus

C43.122 Malignant melanoma of left lower eyelid, including canthus




Revisions from MA08.059d
06/04/2018This policy has undergone a routine review and the medical necessity criteria have been revised to reflect the United States Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia.

Advanced renal cell carcinoma was added as a new covered indication.

The following diagnosis code has been removed from the policy:
C45.0 Mesothelioma of pleura

Revisions from MA08.059c
09/06/2017This version of the policy will become effective 09/06/2017.

This policy has been updated to include information regarding the Company's Dosing and Frequency Program.

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and NCCN compendia.

Policy criteria were updated to include new NCCN criteria for melanoma and new indications: malignant pleural mesothelioma and small cell lung cancer.

Revisions from MA08.059b
07/05/2016
This version of the policy will become effective 07/05/2016.

This policy has been updated to include information regarding the Company's Dosing and Frequency Program.

This policy has been updated to communicate the following newly FDA- and NCCN-approved indications:
  • Ipilimumab (Yervoy®) for adjunctive therapy in Stage III melanoma
  • Nivolumab (Opdivo®) in combination with ipilimumab (Yervoy®) for the treatment unresectable or metastatic melanoma

This policy also communicates the availability of the "Ipilimumab (Yervoy®) Adjuvant Patient Program for Melanoma" which provides free Ipilimumab (Yervoy®) from the Pharmaceutical Company for adjuvant therapy in Stage III melanoma. The treating professional provider should enroll the member in this program.

Revisions from MA08.059a
06/03/2015
This policy has been updated to communicate the Medically Necessary coverage for the treatment of melanoma, as well as, the treatment of brain metastases when the primary tumor is melanoma.

Revisions from MA08.059
01/01/2015This is a new policy.






Version Effective Date: 12/30/2019
Version Issued Date: 12/30/2019
Version Reissued Date: N/A