vp-0148
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Yervoy™ (ipilimumab) (Intravenous)

Policy Number: VP-0148

Last Review Date: 07/05/2022

Date of Origin: 11/28/2011

Dates Reviewed: 12/2011, 03/2012, 06/2012, 09/2012, 12/2012, 05/2013, 06/2013, 09/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 08/2015, 10/2015, 11/2015, 02/2016, 05/2016, 08/2016, 11/2016, 01/2017, 05/2017, 08/2017, 11/2017, 02/2018, 05/2018, 08/2018, 12/2018, 03/2019, 06/2019, 09/2019, 12/2019, 03/2020, 04/2020, 6/2020, 09/2020, 11/2020, 03/2021, 06/2021, 09/2021, 12/2021, 03/2022, 06/2022, 07/2022

FOR PEEHIP Members Only -Coverage excludes the provider-administered medication(s) outlined in this drug policy from being accessed through a specialty pharmacy. It must be obtained through buy and bill.

I. Length of Authorization 1,5,6,8-12,17-19,20,24,27-29,31,33,39-42,44

Coverage will be provided for six (6) months and may be renewed (unless otherwise specified).

  • The following indications may be authorized up to a maximum of twelve (12) weeks of therapy and may NOT be renewed (coverage may be extended to 16 weeks if 4 doses were not administered within the 12 week time frame):
    • Colorectal Cancer (subsequent therapy/disease progression)
    • Appendiceal Adenocarcinoma (subsequent therapy/disease progression)
    • CNS metastases from Melanoma (combination therapy with nivolumab)
    • Cutaneous Melanoma (first-line or subsequent therapy)

* Requests for Cutaneous Melanoma may be renewed if the patient meets the provisions for re-induction therapy.

    • Hepatocellular Carcinoma
    • Renal Cell Carcinoma
    • Small Bowel Adenocarcinoma
    • Ampullary Adenocarcinoma
    • Uveal Melanoma
  • The following indications may be renewed up to a maximum of two (2) years of therapy:
    • Non-Small Cell Lung Cancer
    • Esophageal Cancer
    • Malignant Peritoneal Mesothelioma
    • Malignant Pleural Mesothelioma

Cutaneous Melanoma (adjuvant treatment – maintenance therapy)

  • Coverage for adjuvant treatment will be provided for six (6) months and may be renewed for up to a maximum of three (3) years of maintenance therapy.

II. Dosing Limits

  1. Quantity Limit (max daily dose) [NDC Unit]:
  • Yervoy 200 mg/40 mL injection:           
    • 5 vials per 84 days (initially up to 5 vials per 21 days x 4 doses)
  • Yervoy 50 mg/10 mL injection:
    • 3 vials per 84 days (initially up to 3 vials per 21 days x 4 doses)
  1. Max Units (per dose and over time) [HCPCS Unit]:

Indication

Billable Units (BU)

Per unit time (days)

HCC

350 BU

21 days x 4 doses

Cutaneous Melanoma, CNS metastases

Initial: 1150 BU

Initial: 21 days x 4 doses

Followed by: 1150 BU

Followed by: 84 days

Uveal Melanoma

1150 BU

21 days x 4 doses

RCC, SBA, Ampullary Adenocarcinoma

150 BU

21 days x 4 doses

CRC, Appendiceal Adenocarcinoma, Esophageal Cancer, MPM, MPeM, NSCLC

150 BU

42 days

III. Initial Approval Criteria 1

Coverage is provided in the following conditions:

  • Patient is at least 18 years of age, unless otherwise indicated; AND

Ampullary Adenocarcinoma ‡ 2

  • Patient’s disease is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR); AND
  • Used in combination with nivolumab; AND
    • Used as first-line therapy for unresectable or metastatic intestinal type disease; OR
    • Used as subsequent therapy for disease progression

Central Nervous System (CNS) Cancer 2,4,8,10,11,27

  • Used for the treatment of brain metastases in patients with BRAF non-specific melanoma; AND
  • Used in combination with nivolumab or as a single agent; AND
    • Used as initial treatment in patients with small asymptomatic brain metastases; OR
    • Used for relapsed limited brain metastases with either stable systemic disease or reasonable systemic treatment options; OR
    • Patient has recurrent limited brain metastases; OR
    • Used for recurrent extensive brain metastases with stable systemic disease or reasonable systemic treatment options

Colorectal Cancer (CRC) † 1,2,19,31,42

  • Patient is at least 12 years of age; AND
  • Patient’s disease must be microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR); AND
  • Patient has not previously received treatment with a checkpoint inhibitor (e.g., nivolumab, pembrolizumab, etc.) Δ; AND
  • Used in combination with nivolumab*; AND
  • Used as subsequent therapy for advanced or metastatic disease that progressed following treatment with one of the following:
  • Fluoropyrimidine-, oxaliplatin-, and/or irinotecan-based chemotherapy † ‡; OR
  • Non-intensive therapy** ; OR
  • Used as primary treatment; AND
  • Used as neoadjuvant therapy for clinical T4b colon cancer; OR
  • Used as neoadjuvant therapy of resectable liver and/or lung metastases; OR
  • Used if resection is contraindicated following neoadjuvant therapy for advanced, locally unresectable, or medically inoperable rectal cancer; OR
  • Used for unresectable (or medically inoperable) or metastatic disease

* Single agent nivolumab should be used in patients who are not candidates for intensive therapy.

** Except if received previous fluoropyrimidine, with improvement in functional status.

Appendiceal Adenocarcinoma – Colon Cancer ‡ 2,31

  • Patient’s disease must be microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR); AND
  • Patient has not previously received treatment with a checkpoint inhibitor (e.g., nivolumab, pembrolizumab, etc.) Δ; AND
  • Used in combination with nivolumab*; AND
    • Used as subsequent therapy for advanced or metastatic disease that progressed following previous oxaliplatin- irinotecan- and/or fluoropyrimidine-based therapy; OR
    • Used as initial therapy for advanced or metastatic disease

* Single agent nivolumab should be used in patients who are not candidates for intensive therapy.

Esophageal Cancer † 1,2,45

  • Patient has esophageal squamous cell carcinoma (ESCC); AND
  • Used as first-line treatment of unresectable advanced or metastatic disease; AND
  • Used in combination with nivolumab

Hepatocellular Carcinoma (HCC) † ‡ 1,2,30

  • Used in combination with nivolumab; AND
  • Used as subsequent therapy for progressive disease; AND
  • Patient has Child-Pugh Class A hepatic impairment; AND
    • Patient was previously treated with sorafenib ; OR
    • Patient has unresectable disease and is not a transplant candidate; OR
    • Patient has liver-confined disease that is inoperable by performance status, comorbidity, or with minimal or uncertain extrahepatic-disease; OR
    • Patient has metastatic disease or extensive liver tumor burden

Renal Cell Carcinoma (RCC) † ‡ 1,2,18

  • Used in combination with nivolumab for clear cell histology; AND
    • Used as first-line therapy in patients with advanced, relapsed, or stage IV disease with poor or intermediate risk; OR
    • Used as first-line therapy in patients with relapsed or stage IV disease with favorable risk; OR
    • Used as subsequent therapy in patients with relapsed or stage IV disease

Malignant Peritoneal Mesothelioma (MPeM) ‡ 2

  • Used in combination with nivolumab; AND
    • Used as subsequent therapy (if not administered first-line); OR
    • Used as first-line therapy; AND
  • Patient has unresectable diffuse disease; OR
  • Patient has unresectable recurrent benign multicystic or well-differentiated papillary disease

*Note: May also be used for pericardial mesothelioma and tunica vaginalis testis mesothelioma.

Malignant Pleural Mesothelioma (MPM) † ‡ Ф 1,2,5,25,26,34,37

  • Used in combination with nivolumab; AND
    • Used as subsequent therapy (if not administered first-line); OR
    • Used as first-line therapy; AND
  • Disease is unresectable or medically inoperable; OR
  • Patient has stage IIIB or IV disease; OR
  • Patient has sarcomatoid or biphasic histology

*Note: May also be used for pericardial mesothelioma and tunica vaginalis testis mesothelioma.

Cutaneous Melanoma † ‡ Ф 1,2,6,17,43

  • Used as first-line therapy for unresectable or metastatic disease in combination with nivolumab ; OR
  • Used as initial therapy for limited resectable local satellite/in-transit recurrence; AND
    • Used as a single-agent; AND
    • Patient has prior exposure to anti-PD-1 therapy (e.g., nivolumab or pembrolizumab); OR
  • Used as subsequent therapy for unresectable or metastatic* disease; AND
    • Used after disease progression or maximum clinical benefit from BRAF-targeted therapy (e.g., dabrafenib/trametinib, vemurafenib/cobimetinib, encorafenib/binimetinib, etc.); AND
      • Used as a single agent in patients at least 12 years of age if not previously used alone or in combination with anti-PD-1 immunotherapy ; OR
      • Used in combination with nivolumab if not previously used or for patients who progress on single agent anti-PD-1 therapy; OR
      • Used in combination with pembrolizumab, if not previously used alone or in combination with anti-PD-1 therapy, for patients who progress on single agent anti-PD-1 therapy; OR
    • Used as re-induction therapy in patients who experienced disease control (i.e., complete or partial response or stable disease) and no residual toxicity from prior use, but subsequently have disease progression/relapse > 3 months after treatment discontinuation; AND
      • Used as a single agent or in combination with anti-PD-1 therapy; AND
      • Patient has completed initial induction ipilimumab therapy (i.e., completion of 4 cycles within a 16 week period); OR
  • Used as a single agent for adjuvant therapy; AND
    • Patient has pathologic involvement of regional lymph nodes of more than 1 mm and has undergone complete resection including total lymphadenectomy ; OR
    • Patient has prior exposure to anti-PD-1 therapy (e.g., nivolumab or pembrolizumab); AND
      • Patient has local satellite/in-transit recurrence and has no evidence of disease (NED) after complete excision ; OR
      • Patient has undergone complete therapeutic lymph node dissection (TLND) and/or complete resection of nodal recurrence ; OR
      • Patient has oligometastatic disease and no evidence of disease following metastasis-directed therapy (i.e., stereotactic ablative therapy or complete resection) or systemic therapy

*Metastatic disease includes stage III unresectable/borderline resectable disease with clinically positive nodes or clinical satellite/in-transit metastases, or as well as unresectable local satellite/in-transit recurrence, unresectable nodal recurrence, and widely disseminated distant metastatic disease.

Uveal Melanoma2,20-23,32

  • Used as a single agent or in combination with nivolumab; AND
  • Patient has distant metastatic disease

Non-Small Cell Lung Cancer (NSCLC) † 1,2,16,24

  • Used for recurrent, advanced, or metastatic disease (excluding locoregional recurrence or symptomatic local disease without evidence of disseminated disease) or mediastinal lymph node recurrence with prior radiation therapy; AND
    • Used as first-line therapy; AND
      • Used for one of the following:
        • Patients with a performance status (PS) 0-1 who have tumors that are negative for actionable molecular biomarkers** and PD-L1 <1%
        • Used in patients with a PS 0-1 who are positive for one of the following molecular biomarkers: EGFR exon 20, KRAS G12C, BRAF V600E, NTRK 1/2/3 gene fusion, MET exon 14 skipping, or RET rearrangement
        • PD-L1 expression positive (PD-L1 ≥1%) tumors, as detected by an FDA or CLIA compliant testv, that are negative for actionable molecular biomarkers**; AND
  • Used in combination with nivolumab; OR
  • Used in combination with nivolumab and platinum-doublet chemotherapy (e.g., pemetrexed and either carboplatin or cisplatin for non-squamous cell histology, or paclitaxel and carboplatin for squamous cell histology, etc.); OR
    • Used as subsequent therapy; AND
      • Used for one of the following:
        • Patients with a PS 0-1 who received prior targeted therapy§ for one of the following molecular biomarkers: EGFR S768I, L861Q, and/or G719X, or ROS1 rearrangement
        • Patients with a PS 0-1 who are positive for one of the following molecular biomarkers: BRAF V600E, NTRK 1/2/3 gene fusion, MET exon 14 skipping, or RET rearrangement; AND
  • Used in combination with nivolumab; OR
  • Used in combination with nivolumab, pemetrexed, and either carboplatin or cisplatin for non-squamous cell histology; OR
  • Used in combination with nivolumab, paclitaxel and carboplatin for squamous cell histology; OR
    • Used as continuation maintenance therapy in combination with nivolumab; AND
      • Patient has achieved a response or stable disease following first-line therapy with nivolumab and ipilimumab with or without chemotherapy

** Note: Actionable molecular genomic biomarkers include EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET exon 14 skipping mutation, and RET rearrangement. If there is insufficient tissue to allow testing for all of EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes.

Small Bowel Adenocarcinoma (SBA) ‡ 2,19,29

  • Patient has advanced or metastatic disease that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR); AND
  • Patient has not previously received treatment with a checkpoint inhibitor (e.g., nivolumab, pembrolizumab, etc.) Δ; AND
  • Used in combination with nivolumab; AND
    • Used as initial therapy; OR
    • Used as subsequent therapy for patients with no prior oxaliplatin exposure in the adjuvant treatment setting and no contraindication to oxaliplatin therapy

v If confirmed using an immunotherapy assay-http://www.fda.gov/CompanionDiagnostics

FDA approved indication(s); Compendia recommended indication; Ф Orphan Drug

Genomic Aberration/Mutational Driver Targeted Therapies

(Note: not all inclusive, refer to guidelines for appropriate use) §

Sensitizing EGFR mutation-positive tumors

ALK rearrangement-positive tumors

ROS1 rearrangement-positive tumors

BRAF V600E-mutation positive tumors

NTRK1/2/3 gene fusion positive tumors

 

  • Afatinib
  • Erlotinib
  • Dacomitinib
  • Gefitinib
  • Osimertinib
  • Amivantamab

(exon-20 insertion)

  • Mobocertinib

(exon-20 insertion)

  • Alectinib
  • Brigatinib
  • Ceritinib
  • Crizotinib
  • Lorlatinib
  • Ceritinib
  • Crizotinib 
  • Entrectinib
  • Lorlatinib
  • Dabrafenib

± trametinib

  • Vemurafenib
  • Larotrectinib
  • Entrectinib

 

PD-L1 tumor expression ≥1%

PD-L1 tumor expression ≥50%

MET exon-14 skipping mutations

RET rearrangement-positive tumors

KRAS G12C mutation positive tumors

 

  • Pembrolizumab
  • Atezolizumab
  • Nivolumab + ipilimumab
  • Pembrolizumab
  • Atezolizumab
  • Nivolumab + ipilimumab
  • Cemiplimab
  • Capmatinib
  • Crizotinib
  • Tepotinib
  • Selpercatinib
  • Cabozantinib
  • Pralsetinib
  • Sotorasib

 

IV. Renewal Criteria ∆ 1,2,6,9-12,17-29,39-41

Coverage may be renewed based upon the following criteria:

  • Patient continues to meet the universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
  • Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: immune-mediated reactions (e.g., colitis, hepatitis, dermatitis/skin adverse reactions, pneumonitis, nephritis/renal dysfunction, endocrinopathies, etc.), severe infusion reactions, complications of allogeneic hematopoietic stem cell transplantation (HSCT), etc.; AND
  • Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
  • Coverage may NOT be renewed for the following indications:
  • Renal Cell Carcinoma
  • Colorectal Cancer (subsequent therapy/disease progression)
  • Appendiceal Adenocarcinoma (subsequent therapy/disease progression)
  • Small Bowel Adenocarcinoma
  • Ampullary Adenocarcinoma
  • Hepatocellular Carcinoma
  • Cutaneous Melanoma (first-line or subsequent therapy)
  • Uveal Melanoma
  • CNS metastases from Melanoma (combination therapy with nivolumab)
  • For the following indications, patient has not exceeded a maximum of two (2) years of therapy:
  • Non-Small Cell Lung Cancer
  • Esophageal Cancer
  • Malignant Peritoneal Mesothelioma
  • Malignant Pleural Mesothelioma

Cutaneous Melanoma (re-induction therapy)

  • Refer to Section III for criteria (see Cutaneous Melanoma – Used for retreatment of disease as re-induction)

Cutaneous Melanoma (adjuvant treatment – maintenance therapy)

  • Patient has not exceeded a maximum of three (3) years of therapy

Non-Small Cell Lung Cancer (continuation maintenance therapy)

  • Refer to Section III for criteria

 

Δ Notes:

  • Patients responding to therapy who relapse ≥ 6 months after discontinuation due to duration (i.e., receipt of 24 months of PD-directed therapy) are eligible to re-initiate checkpoint inhibitor therapy.
  • Patients who complete adjuvant therapy and progress ≥ 6 months after discontinuation are eligible to re-initiate checkpoint inhibitor therapy for metastatic disease.
  • Patients whose tumors, upon re-biopsy, demonstrate a change in actionable mutation (e.g., MSS initial biopsy; MSI-H subsequent biopsy) may be eligible to re-initiate checkpoint inhibitor therapy and will be evaluated on a case-by-case basis.

V. Dosage/Administration 1,5,6,8-12,17-29,31,33,34,38,39-42,44

Indication

Dose

Renal Cell Carcinoma (RCC), Small Bowel Adenocarcinoma (SBA), & Ampullary Adenocarcinoma

Administer 1 mg/kg intravenously every 3 weeks for a total of 4 doses (given in combination with nivolumab, then follow with nivolumab monotherapy)

CNS metastases from Melanoma

Single agent:

    • Initial: Administer 10 mg/kg intravenously every 3 weeks for 4 doses
    • Subsequent (starting at week 24): Administer 10 mg/kg intravenously every 12 weeks until disease progression or unacceptable toxicity

In combination with nivolumab:

    • Administer 3 mg/kg intravenously every 3 weeks for 4 doses (given in combination with nivolumab, then follow with nivolumab monotherapy)

Colorectal Cancer (CRC) & Appendiceal Adenocarcinoma

Primary/initial treatment

    • Administer 1 mg/kg intravenously every 6 weeks, with nivolumab every 2 weeks, until disease progression or unacceptable toxicity

Subsequent therapy/disease progression

    • Administer 1 mg/kg intravenously every 3 weeks for a total of 4 doses (given in combination with nivolumab, then follow with nivolumab monotherapy)

Esophageal Cancer

Administer 1 mg/kg intravenously every 6 weeks (given in combination with nivolumab) until disease progression or unacceptable toxicity for up to 2 years

Hepatocellular Carcinoma (HCC)

Administer 3 mg/kg intravenously every 3 weeks for a total of 4 doses (given in combination with nivolumab, then follow with nivolumab monotherapy)

Malignant Pleural Mesothelioma (MPM) & Malignant Peritoneal Mesothelioma (MPeM)

Administer 1 mg/kg intravenously every 6 weeks (given in combination with nivolumab) until disease progression or unacceptable toxicity for up to 2 years

Cutaneous Melanoma (excluding adjuvant therapy)

Single agent or in combination with nivolumab:

    • Administer 3 mg/kg intravenously every 3 weeks for a maximum of 4 doses (when given in combination with nivolumab, follow with nivolumab monotherapy)

In combination with pembrolizumab as subsequent therapy:

    • Administer 1 mg/kg intravenously every 3 weeks for a maximum of 4 doses (given in combination with pembrolizumab, then follow with pembrolizumab monotherapy)

Cutaneous Melanoma (adjuvant therapy)

    • Initial: Administer 10 mg/kg intravenously every 3 weeks for 4 doses
    • Maintenance: Administer 10 mg/kg intravenously every 12 weeks for up to 3 years

Uveal Melanoma

Single agent:

    • Administer 3 mg/kg or 10mg/kg intravenously every 3 weeks for 4 doses

In combination with nivolumab:

    • Administer 3 mg/kg intravenously 3 weeks for 4 doses (given in combination with nivolumab, then follow with nivolumab monotherapy)

Non-Small Cell Lung Cancer (NSCLC)

In combination with nivolumab:

    • Administer 1 mg/kg intravenously every 6 weeks (given in combination with nivolumab every 2 weeks), until disease progression or unacceptable toxicity for up to 2 years

In combination with nivolumab and platinum-doublet chemotherapy:

    • Administer 1 mg/kg intravenously every 6 weeks (given in combination with nivolumab every 3 weeks and 2 cycles of histology-based platinum-doublet chemotherapy every 3 weeks), until disease progression or unacceptable toxicity for up to 2 years

* All treatments given for a maximum of 4 doses must be administered within 16 weeks of the first dose.

VI. Billing Code/Availability Information

HCPCS Code:

  • J9228 – Injection, ipilimumab, 1 mg: 1 billable unit = 1 mg

NDC(s):

  • Yervoy 200 mg/40 mL injection (single-dose vial): 00003-2328-xx
  • Yervoy 50 mg/10 mL injection (single-dose vial): 00003-2327-xx

VII. References

  1. Yervoy [package insert]. Princeton, NJ; Bristol Meyers Squib; May 2022. Accessed June 2022.
  2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) ipilimumab. National Comprehensive Cancer Network, 2022. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed June 2022.
  3. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Small Cell Lung Cancer. Version 2.2022. National Comprehensive Cancer Network, 2022. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed May 2022.
  4. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Central Nervous System Cancers. Version 2.2021. National Comprehensive Cancer Network, 2022. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed May 2022.
  5. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Malignant Pleural Mesothelioma. Version 1.2022. National Comprehensive Cancer Network, 2022. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed May 2022.
  6. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19; 363(8):711-23.
  7. Wilgenhof S, Du Four S, Vandenbroucke F, et al. Single-center experience with ipilimumab in an expanded access program for patients with pretreated advanced melanoma. J Immunother. 2013 Apr; 36(3):215-22.
  8. 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 May; 13(5):459-65.
  9. Antonia SJ, López-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-895.
  10. Tawbi HA, Forsyth PAJ, Algazi AP, et al. Efficacy and safety of nivolumab (NIVO) plus ipilimumab (IPI) in patients with melanoma (MEL) metastatic to the brain: Results of the phase II study CheckMate 204. Journal of Clinical Oncology 35, no. 15_suppl (May 2017) 9507-9507.
  11. Long GV, Atkinson V, Menzies AM, et al. A randomized phase II study of nivolumab or nivolumab combined with ipilimumab in patients (pts) with melanoma brain metastases (mets): The Anti-PD1 Brain Collaboration (ABC). Journal of Clinical Oncology 35, no. 15_suppl (May 2017) 9508-9508.
  12. 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; 378:2093-2104.
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  4. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Non-Small Cell Lung Cancer. Version 3.2022. National Comprehensive Cancer Network, 2022. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed May 2022.
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  5. Long GV, Atkinson V, Lo S, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018 May;19(5):672-681. doi: 10.1016/S1470-2045(18)30139-6. Epub 2018 Mar 27.
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  10. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Melanoma: Uveal. Version 2.2022. National Comprehensive Cancer Network, 2022. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed May 2022.
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  14. Reck M, Ciuleanu T-E, Dols MC, et al. Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (chemo) vs 4 cycles chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA [abstract]. J Clin Oncol 2020;38:Abstract 9501-9501.
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  1. Lenz HJ, Lonardi S, Zagonel V, et al. Nivolumab (NIVO) + low-dose ipilimumab (IPI) as first-line (1L) therapy in microsatellite instability-high/DNA mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Clinical update [abstract]. Journal of Clinical Oncology 2019;37:3521-3521.
  2. Hodi FS, Chiarion-Sileni V, Gonzalez R, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Nov;19(11):1480-1492. doi: 10.1016/S1470-2045(18)30700-9. Epub 2018 Oct 22. Erratum in: Lancet Oncol. 2018 Dec;19(12):e668. Erratum in: Lancet Oncol. 2018 Nov;19(11):e581.
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  4. Doki Y, Ajani JA, Kato K, et al. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med. 2022 Feb 3;386(5):449-462. doi: 10.1056/NEJMoa2111380.

Appendix 1 – Covered Diagnosis Codes

ICD-10

ICD-10 Description

C15.3

Malignant neoplasm of upper third of esophagus

C15.4

Malignant neoplasm of middle third of esophagus

C15.5

Malignant neoplasm of lower third of esophagus

C15.8

Malignant neoplasm of overlapping sites of esophagus

C15.9

Malignant neoplasm of esophagus, unspecified

C16.0

Malignant neoplasm of cardia

C17.0

Malignant neoplasm of duodenum

C17.1

Malignant neoplasm of jejunum

C17.2

Malignant neoplasm of ileum

C17.3

Meckel's diverticulum, malignant

C17.8

Malignant neoplasm of overlapping sites of small intestine

C17.9

Malignant neoplasm of small intestine, unspecified

C18.0

Malignant neoplasm of cecum

C18.1

Malignant neoplasm of appendix

C18.2

Malignant neoplasm of ascending colon

C18.3

Malignant neoplasm of hepatic flexure

C18.4

Malignant neoplasm of transverse colon

C18.5

Malignant neoplasm of splenic flexure

C18.6

Malignant neoplasm of descending colon

C18.7

Malignant neoplasm of sigmoid colon

C18.8

Malignant neoplasm of overlapping sites of colon

C18.9

Malignant neoplasm of colon, unspecified

C19

Malignant neoplasm of rectosigmoid junction

C20

Malignant neoplasm of rectum

C21.8

Malignant neoplasm of overlapping sites of rectum, anus and anal canal

C22.0

Liver cell carcinoma

C22.8

Malignant neoplasm of liver, primary, unspecified as to type

C22.9

Malignant neoplasm of liver, not specified as primary or secondary

C24.1

Malignant neoplasm of ampulla of Vater

C33

Malignant neoplasm of trachea

C34.00

Malignant neoplasm of unspecified main bronchus

C34.01

Malignant neoplasm of right main bronchus

C34.02

Malignant neoplasm of left main bronchus

C34.10

Malignant neoplasm of upper lobe, unspecified bronchus or lung

C34.11

Malignant neoplasm of upper lobe, right bronchus or lung

C34.12

Malignant neoplasm of upper lobe, left bronchus or lung

C34.2

Malignant neoplasm of middle lobe, bronchus or lung

C34.30

Malignant neoplasm of lower lobe, unspecified bronchus or lung

C34.31

Malignant neoplasm of lower lobe, right bronchus or lung

C34.32

Malignant neoplasm of lower lobe, left bronchus or lung

C34.80

Malignant neoplasm of overlapping sites of unspecified bronchus and lung

C34.81

Malignant neoplasm of overlapping sites of right bronchus and lung

C34.82

Malignant neoplasm of overlapping sites of left bronchus and lung

C34.90

Malignant neoplasm of unspecified part of unspecified bronchus or lung

C34.91

Malignant neoplasm of unspecified part of right bronchus or lung

C34.92

Malignant neoplasm of unspecified part of left bronchus or lung

C43.0

Malignant melanoma of lip

C43.10

Malignant melanoma of unspecified eyelid, including canthus

C43.11

Malignant melanoma of right eyelid, including canthus

C43.12

Malignant melanoma of left eyelid, including canthus

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

C43.20

Malignant melanoma of unspecified ear and external auricular canal

C43.21

Malignant melanoma of right ear and external auricular canal

C43.22

Malignant melanoma of left ear and external auricular canal

C43.30

Malignant melanoma of unspecified part of face

C43.31

Malignant melanoma of nose

C43.39

Malignant melanoma of other parts of face

C43.4

Malignant melanoma of scalp and neck

C43.51

Malignant melanoma of anal skin

C43.52

Malignant melanoma of skin of breast

C43.59

Malignant melanoma of other part of trunk

C43.60

Malignant melanoma of unspecified upper limb, including shoulder

C43.61

Malignant melanoma of right upper limb, including shoulder

C43.62

Malignant melanoma of left upper limb, including shoulder

C43.70

Malignant melanoma of unspecified lower limb, including hip

C43.71

Malignant melanoma of right lower limb, including hip

C43.72

Malignant melanoma of left lower limb, including hip

C43.8

Malignant melanoma of overlapping sites of skin

C43.9

Malignant melanoma of skin, unspecified

C45.0

Mesothelioma of pleura

C45.1

Mesothelioma of peritoneum

C45.2

Mesothelioma of pericardium

C45.7

Mesothelioma of other sites

C45.9

Mesothelioma, unspecified

C64.1

Malignant neoplasm of right kidney, except renal pelvis

C64.2

Malignant neoplasm of left kidney, except renal pelvis

C64.9

Malignant neoplasm of unspecified kidney, except renal pelvis

C65.1

Malignant neoplasm of right renal pelvis

C65.2

Malignant neoplasm of left renal pelvis

C65.9

Malignant neoplasm of unspecified renal pelvis

C69.30

Malignant neoplasm of unspecified choroid

C69.31

Malignant neoplasm of right choroid

C69.32

Malignant neoplasm of left choroid

C69.40

Malignant neoplasm of unspecified ciliary body

C69.41

Malignant neoplasm of right ciliary body

C69.42

Malignant neoplasm of left ciliary body

C69.60

Malignant neoplasm of unspecified orbit

C69.61

Malignant neoplasm of right orbit

C69.62

Malignant neoplasm of left orbit

C78.00

Secondary malignant neoplasm of unspecified lung

C78.01

Secondary malignant neoplasm of right lung

C78.02

Secondary malignant neoplasm of left lung

C78.6

Secondary malignant neoplasm of retroperitoneum and peritoneum

C78.7

Secondary malignant neoplasm of liver and intrahepatic bile duct

C79.31

Secondary malignant neoplasm of brain

D37.8

Neoplasm of uncertain behavior of other specified digestive organs

D37.9

Neoplasm of uncertain behavior of digestive organ, unspecified

Z85.00

Personal history of malignant neoplasm of unspecified digestive organ

Z85.01

Personal history of malignant neoplasm of esophagus

Z85.038

Personal history of other malignant neoplasm of large intestine

Z85.068

Personal history of other malignant neoplasm of small intestine

Z85.118

Personal history of other malignant neoplasm of bronchus and lung

Z85.820

Personal history of malignant melanoma of skin

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A

Medicare Part B Administrative Contractor (MAC) Jurisdictions

Jurisdiction

Applicable State/US Territory

Contractor

E (1)

CA, HI, NV, AS, GU, CNMI

Noridian Healthcare Solutions, LLC

F (2 & 3)

AK, WA, OR, ID, ND, SD, MT, WY, UT, AZ

Noridian Healthcare Solutions, LLC

5

KS, NE, IA, MO

Wisconsin Physicians Service Insurance Corp (WPS)

6

MN, WI, IL

National Government Services, Inc. (NGS)

H (4 & 7)

LA, AR, MS, TX, OK, CO, NM

Novitas Solutions, Inc.

8

MI, IN

Wisconsin Physicians Service Insurance Corp (WPS)

N (9)

FL, PR, VI

First Coast Service Options, Inc.

J (10)

TN, GA, AL

Palmetto GBA, LLC

M (11)

NC, SC, WV, VA (excluding below)

Palmetto GBA, LLC

L (12)

DE, MD, PA, NJ, DC (includes Arlington & Fairfax counties and the city of Alexandria in VA)

Novitas Solutions, Inc.

K (13 & 14)

NY, CT, MA, RI, VT, ME, NH

National Government Services, Inc. (NGS)

15

KY, OH

CGS Administrators, LLC