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Yervoy™ (ipilimumab)

Policy Number: VP-0148

​

 Intravenous

Last Review Date: 07/02/2024

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, 09/2022, 12/2022, 03/2023, 06/2023, 09/2023, 12/2023, 03/2024, 07/2024

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.

  1. Length of Authorization ∆ 1,5,6,8-12,17-19,20-24,27-29,31,33,39-42,44,46-49,53,54

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

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

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

  • Cutaneous Melanoma (adjuvant therapy in combination with nivolumab)
  • Small Bowel Adenocarcinoma
  • Uveal Melanoma
  • The following indications may be renewed up to a maximum of 2 years of therapy (18 doses):
    • Biliary Tract Cancers
    • Bone Cancer
    • Esophageal and Esophagogastric/Gastroesophageal Junction Cancer (first-line therapy for squamous cell carcinoma)
    • Kaposi Sarcoma
    • Non-Small Cell Lung Cancer
    • Peritoneal Mesothelioma (initial therapy)**
    • Pleural Mesothelioma (initial therapy)**

** Including pericardial mesothelioma and tunica vaginalis testis mesothelioma

Gastric Cancer

  • Coverage will be provided for a maximum of 12 weeks (2 doses) and may not be renewed for neoadjuvant or perioperative therapy  
  • Coverage will be provided for a maximum of 16 weeks (3 doses) and may not be renewed for early-stage disease following endoscopic resection, first line therapy, or subsequent therapy

MSI-H/dMMR Esophageal and Esophagogastric/Gastroesophageal Junction Cancer

  • Coverage will be provided for a maximum of 12 weeks of therapy (2 doses) and may not be renewed for neoadjuvant or perioperative therapy
  • Coverage will be provided for a maximum of 16 weeks (3 doses) and may not be renewed for relieving dysphagia, first line therapy, or subsequent therapy

Cutaneous Melanoma (single agent adjuvant treatment)

  • Coverage will be provided for 6 months and may be renewed for up to a maximum of 3 years of maintenance therapy (17 doses total [initial and maintenance doses combined]).

Cutaneous Melanoma (neoadjuvant treatment in combination with nivolumab)

  • Coverage will be provided for a maximum of 6 weeks of therapy (2 doses) and may not be renewed.
  1. 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)

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

150 billable units

21 days x 4 doses

Colorectal Cancer (CRC), Appendiceal Adenocarcinoma

150 billable units

21 days

Pleural Mesothelioma (PM), Peritoneal Mesothelioma (PeM), Pericardial Mesothelioma, Tunica Vaginalis Testis Mesothelioma, Soft Tissue Sarcoma, MSI-H/dMMR Esophageal, and Esophagogastric/ Gastroesophageal Junction Cancer, Gastric Cancer, Biliary Tract Cancers, Bone Cancer, & Kaposi Sarcoma, Esophageal and Esophagogastric/ Gastroesophageal Junction Cancer, NSCLC

150 billable units

42 days

Merkel Cell Carcinoma

Initial

350 billable units

21 days x 4 doses

Maintenance

150 billable units

42 days

Hepatocellular Carcinoma (HCC)

350 billable units

21 days x 4 doses

CNS Cancers, Cutaneous Melanoma

Initial

1150 billable units

21 days x 4 doses

Maintenance

1150 billable units

84 days

Uveal Melanoma

1150 billable units

21 days x 4 doses
  1. 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 has microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) disease as determined by an FDA-approved or CLIA-compliant testv; 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

Biliary Tract Cancers (Gallbladder Cancer or Intra-/Extra-Hepatic Cholangiocarcinoma) ‡ 2,46

  • Used in combination with nivolumab; AND
  • Patient has tumor mutational burden-high (TMB-H) [≥ 10 mutations/megabase (mut/Mb)] disease as determined by an FDA-approved or CLIA-compliant testv; AND
    • Used as subsequent treatment for progression on or after systemic treatment for unresectable, resected gross residual (R2), or metastatic disease; AND
      • Disease is refractory to standard therapies or there are no standard treatment options available; OR
    • Used as neoadjuvant therapy for resectable locoregionally advanced (**NOTE: Only applies to Gallbladder Cancer); AND
      • Patient has incidental finding of suspicious mass during surgery where hepatobiliary surgery expertise is unavailable; OR
      • Patient has incidental finding on pathologic review (cystic duct node positive); OR
      • Patient has mass on imaging

Bone Cancer ‡ 2,46

  • Patient has one of the following: Ewing sarcoma, Chondrosarcoma (excluding mesenchymal chondrosarcoma), Osteosarcoma, or Chordoma; AND
  • Patient has tumor mutation burden-high (TMB-H) [≥ 10 mutations/megabase (mut/Mb)] disease as determined by an FDA-approved or CLIA-compliant testv; AND
  • Used in combination with nivolumab; AND
  • Patient has unresectable or metastatic disease that progressed following prior treatment; AND
  • Patient has no satisfactory alternative treatment options

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 has microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) disease OR polymerase epsilon/delta (POLE/POLD1) mutation  as determined by an FDA-approved or CLIA-compliant testv; AND
  • Used in combination with nivolumab*; AND
  • Used as subsequent therapy; AND
  • Patient has metastatic, unresectable, or medically inoperable disease; OR
  • Used as primary or initial treatment; AND
  • Used for isolated pelvic/anastomotic recurrence of rectal cancer; OR
  • Patient has T3, N Any; T1-2, N1-2; T4, N Any rectal cancer; OR
  • Patient has metastatic, unresectable, or medically inoperable disease; OR
  • Used as neoadjuvant therapy; AND
  • Patient has clinical T4b colon cancer (dMMR/MSI-H disease ONLY); OR
  • Patient has resectable liver and/or lung metastases

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

Appendiceal Adenocarcinoma – Colon Cancer ‡ 2,31

  • Patient has microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) disease OR polymerase epsilon/delta (POLE/POLD1) mutation as determined by an FDA-approved or CLIA-compliant testv; AND
  • Used in combination with nivolumab*; AND
  • Used for advanced or metastatic disease; AND
    • Used as primary or initial treatment; OR
    • Used as subsequent treatment

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

Esophageal Cancer and Esophagogastric/Gastroesophageal Junction Cancers † ‡ 1,2,45,53

  • Used in combination with nivolumab; AND
    • Used as first-line therapy; AND
      • Patient has squamous cell carcinoma †; AND
        • Patient is not a surgical candidate or has unresectable advanced, recurrent, or metastatic disease; OR
      • Patient has adenocarcinoma; AND
        • Patient is not a surgical candidate or has unresectable locally advanced, recurrent, or metastatic disease; AND
        • Patient has microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) disease as determined by an FDA-approved or CLIA-compliant testv; OR
          • Used as subsequent therapy; AND
      • Patient is not a surgical candidate or has unresectable locally advanced, recurrent, or metastatic disease; AND
      • Patient has microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) disease as determined by an FDA-approved or CLIA-compliant testv; OR
    • Used as neoadjuvant or perioperative therapy; AND
      • Patient has adenocarcinoma; AND
      • Used as primary treatment for patients who are medically fit for surgery with cT2, N0 (high-risk lesions: lymphovascular invasion, ≥ 3cm, poorly differentiated), cT1b-cT2, N+ or cT3-cT4a, Any N disease; AND
      • Patient has microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) disease as determined by an FDA-approved or CLIA-compliant testv; OR
    • Used as induction systemic therapy for relieving dysphagia; AND
      • Patient has microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) disease as determined by an FDA-approved or CLIA-compliant testv; AND
      • Patient is medically fit and planned for esophagectomy with cT2, N0 (high-risk lesions: lymphovascular invasion, ≥ 3 cm, poorly differentiated), cT1b-cT2, N+ or cT3-cT4a, Any N disease

Gastric Cancer ‡ 2,54

  • Used in combination with nivolumab; AND
  • Patient has microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) disease as determined by an FDA-approved or CLIA-compliant testv; AND
    • Used as first-line or subsequent therapy; AND
      • Patient is not a surgical candidate or has unresectable locally advanced, recurrent, or metastatic disease; OR
    • Used as neoadjuvant or perioperative therapy; AND
      • Used as primary treatment prior to surgery for potentially resectable locoregional disease (cT2 or higher, any N) in patients who are medically fit for surgery; OR
    • Used as systemic therapy for early-stage disease; AND
      • Patient has endoscopic features suggestive of deep submucosal invasion including converging folds, irregular surface pattern, and ulceration in a large gastric mass with favorable histology; AND
      • Patient has completed an endoscopic resection

Hepatocellular Carcinoma (HCC) † ‡ 1,2

  • Used in combination with nivolumab; AND
  • Used as subsequent therapy; AND
    • Patient was previously treated with sorafenib †; OR
    • Patient has liver-confined, unresectable disease and deemed ineligible for transplant; OR
    • Patient has extrahepatic/metastatic disease and deemed ineligible for resection, transplant, or locoregional therapy

Kaposi Sarcoma ‡ 2,47

  • Used in combination with nivolumab as subsequent therapy; AND
  • Patient has classic disease; AND
  • Used for relapsed/refractory advanced cutaneous, oral, visceral, or nodal disease; AND
  • Disease progressed on or did not respond to first-line therapy; AND
  • Disease progressed on alternate first-line therapy

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 poor or intermediate risk advanced, relapsed, or stage IV disease; OR
    • Used as first-line therapy in patients with favorable risk relapsed or stage IV disease; OR
    • Used as subsequent therapy in patients with relapsed or stage IV disease ∆

Peritoneal Mesothelioma (PeM)* ‡ 2,56

  • Used in combination with nivolumab; AND
    • Used as subsequent therapy (if chemotherapy was administered first-line); OR
    • Used as first-line therapy; AND
      • Patient has unicavitary disease with epithelioid histology; AND
  • Used as adjuvant treatment for medically operable disease, following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC); AND
    • Patient has surgical or pathologic high-risk features** and no neoadjuvant therapy was given; OR
  • Patient has medically inoperable disease and/or complete cytoreduction not achieved (including high-risk features**); OR
  • Patient has disease recurrence after prior CRS + HIPEC if no previous adjuvant systemic therapy was given; OR
    • Patient has biphasic/sarcomatoid histology or bicavitary disease

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

** High-risk features include Ki-67 >9%, nodal metastasis, high tumor burden (Peritoneal Cancer Index [PCI] >17), completeness of cytoreduction (CC) score >1, biphasic disease, or bicavitary disease

Pleural Mesothelioma (PM)* † ‡ Ф 1,2,5,25,26,34,37

  • Used in combination with nivolumab; AND
    • Used as subsequent therapy (if chemotherapy was administered first-line); OR
    • Used as first-line therapy; AND
  • Patient has clinical stage IIIB or IV disease; OR
  • Patient has sarcomatoid or biphasic histology; OR
  • Disease is medically inoperable or unresectable; OR
  • Patient has clinical stage I-IIIA disease with epithelioid histology and did not receive induction chemotherapy

*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 †; AND
    • Patient is at least 12 years of age; AND
    • Used as a single agent or in combination with nivolumab; OR
  • Used as subsequent therapy for unresectable or metastatic* disease; AND
    • Used after disease progression, intolerance, and/or projected risk of progression with 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 therapy; OR
      • Used in combination with nivolumab in patients at least 12 years of age 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 adjuvant treatment; AND
    • Used as a single agent; 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 resectable disease limited to nodal recurrence following excision and complete therapeutic lymph node dissection (TLND)‡; OR
        • Patient has oligometastatic disease and no evidence of disease (NED) following metastasis-directed therapy (i.e., complete resection, stereotactic ablative therapy or T-VEC/intralesional therapy) OR following systemic therapy followed by resection ‡; OR
    • Used in combination with nivolumab; AND
      • Patient has oligometastatic disease and NED following metastasis-directed therapy (i.e., complete resection, stereotactic ablative therapy or T-VEC/intralesional therapy) OR following systemic therapy followed by resection; OR
  • Used as neoadjuvant therapy; AND
    • Used in combination with nivolumab; AND
      • Patient stage III disease; AND
        • Used as primary treatment for clinically positive, resectable nodal disease; OR
        • Used for limited resectable disease with clinical satellite/in-transit metastases; OR
      • Patient has limited resectable local satellite/in-transit recurrence; OR
      • Patient has resectable disease limited to nodal recurrence

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

Uveal Melanoma ‡ 2,20-23,32

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

Merkel Cell Carcinoma ‡ 2,50,51

  • Used for M1 disseminated disease; AND
  • Used as a single agent or in combination with nivolumab; AND
  • Patient progressed on anti-PD-L1 or anti-PD-1 therapy OR anti-PD-L1 or anti-PD-1 therapy is contraindicated

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%
        • 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, RET rearrangement, or ERBB2 (HER2)
        • 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 one of the following:
        • Nivolumab
        • 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 are positive for one of the following molecular biomarkers and have received prior targeted therapy§: EGFR exon 19 deletion or exon 21 L858R tumors, EGFR S768I, L861Q, and/or G719X, ALK rearrangement, 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 one of the following:
        • Nivolumab
        • Nivolumab, pemetrexed, and either carboplatin or cisplatin for non-squamous cell histology
        • 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, RET, and ERBB2 (HER2). Complete genotyping for EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, and ERBB2 (HER2) via biopsy and/or plasma testing. If a clinically actionable marker is found, it is reasonable to start therapy based on the identified marker. Treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes.

¥ May also be used for patients with KRAS G12C mutation positive tumors.

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) OR polymerase epsilon/delta (POLE/POLD1) mutation as detected by an FDA or CLIA compliant testv; AND
  • Used in combination with nivolumab

Soft Tissue Sarcoma ‡ 2,46,52

  • Extremity/Body Wall, Head/Neck* or Retroperitoneal/Intra-Abdominal**
    • Used in combination with nivolumab; AND
    • Used as subsequent therapy; AND
      • Patient has myxofibrosarcoma, undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma, cutaneous angiosarcoma, or undifferentiated sarcomas; OR
      • Patient has tumor mutational burden-high (TMB-H) [≥ 10 mutations/megabase (mut/Mb)] disease as determined by an FDA-approved or CLIA-compliant testv; AND
    • Patient has no satisfactory alternative treatment options
  • Pleomorphic Rhabdomyosarcoma
    • Used in combination with nivolumab; AND
    • Used as subsequent therapy; AND
    • Patient has tumor mutational burden-high (TMB-H) [≥ 10 mutations/megabase (mut/Mb)] disease as determined by an FDA-approved or CLIA-compliant testv; AND
    • Patient has no satisfactory alternative treatment options
  • Angiosarcoma
    • Used in combination with nivolumab

*For atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) of the extremity, abdominal wall, trunk that was initially diagnosed as ALT/WDLPS and shows evidence of de-differentiation, treat as other soft tissue sarcomas.

**For well-differentiated liposarcoma (WDLPS-retroperitoneum, paratesticular) with or without evidence of de-differentiation, treat as other soft tissue sarcomas

v If confirmed using an FDA approved 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)

EGFR exon 19 deletion or exon 21 L858R tumors

EGFR S768I, L861Q, and/or G719X mutation positive tumors

EGFR exon 20 insertion mutation positive tumors

NTRK1/2/3 gene fusion positive tumors
  • Afatinib
  • Erlotinib
  • Dacomitinib
  • Gefitinib
  • Osimertinib
  • Amivantamab
  • Afatinib
  • Erlotinib
  • Dacomitinib
  • Gefitinib
  • Osimertinib
  • Amivantamab
  • Amivantamab
  • Larotrectinib
  • Entrectinib

ALK rearrangement-positive tumors

ROS1 rearrangement-positive tumors

BRAF V600E-mutation positive tumors

ERBB2 (HER2) mutation positive tumors
  • Alectinib
  • Brigatinib
  • Ceritinib
  • Crizotinib
  • Lorlatinib
  • Ceritinib
  • Crizotinib 
  • Entrectinib
  • Lorlatinib
  • Repotrectinib
  • Dabrafenib ± trametinib
  • Encorafenib + binimetinib
  • Vemurafenib
  • Fam-trastuzumab deruxtecan-nxki
  • Ado-trastuzumab emtansine

PD-L1 tumor

expression ≥ 1%

MET exon-14 skipping mutations

RET rearrangement-positive tumors

KRAS G12C mutation positive tumors
  • Pembrolizumab
  • Atezolizumab
  • Nivolumab + ipilimumab
  • Cemiplimab
  • Tremelimumab + durvalumab
  • Capmatinib
  • Crizotinib
  • Tepotinib
  • Selpercatinib
  • Cabozantinib
  • Pralsetinib
  • Sotorasib
  • Adagrasib
  1. Renewal Criteria ∆ 1,2,6,9-12,17-29,39-41,46-49,53,54

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: severe immune-mediated adverse reactions (e.g., colitis, hepatitis, dermatitis/rash, pneumonitis, nephritis/renal dysfunction, endocrinopathies, etc.), severe infusion-related 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:
  • Ampullary Adenocarcinoma
  • Colorectal Cancer (subsequent therapy)
  • Appendiceal Adenocarcinoma (subsequent therapy)
  • CNS Cancer (combination therapy with nivolumab)
  • MSI-H/dMMR Esophageal and Esophagogastric/Gastroesophageal Junction Cancer
  • Gastric Cancer
  • Hepatocellular Carcinoma
  • Renal Cell Carcinoma
  • Cutaneous Melanoma (first-line or subsequent therapy)

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

  • Cutaneous Melanoma (neoadjuvant or adjuvant therapy in combination with nivolumab)
  • Small Bowel Adenocarcinoma
  • Uveal Melanoma
  • For the following indications, patient has not exceeded a maximum of 2 years of therapy (18 doses):
  • Biliary Tract Cancer
  • Bone Cancer
  • Esophageal and Esophagogastric/Gastroesophageal Junction Cancer (first-line therapy for squamous cell carcinoma)
  • Kaposi Sarcoma
  • Non-Small Cell Lung Cancer
  • Peritoneal Mesothelioma (initial therapy)**
  • Pleural Mesothelioma (initial therapy)**

** Including pericardial mesothelioma and tunica vaginalis testis 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 (single agent adjuvant treatment – maintenance therapy)

  • Patient has not exceeded a maximum of 3 years of therapy (17 doses total [initial and maintenance doses combined])

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.
  • Patients diagnosed with Renal Cell Carcinoma with clear cell histology who have received previous immuno-oncology therapy may be eligible for treatment with ipilimumab as subsequent therapy and will be evaluated on a case-by-case basis.
  1. Dosage/Administration ∆ 1,5,6,8-12,17-29,31,33,34,38-42,44,46-55,57-60

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 on the same day, then follow with nivolumab monotherapy)

Biliary Tract Cancers, Bone Cancer, & Kaposi Sarcoma

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 24 months (2 years)

CNS Cancers

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 on the same day, then follow with nivolumab monotherapy)

Colorectal Cancer (CRC)

Neoadjuvant therapy

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

Primary/initial treatment

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

Subsequent therapy

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

Appendiceal Adenocarcinoma

Primary/initial treatment

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

Subsequent therapy

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

Esophageal and Esophagogastric/ Gastroesophageal Junction Cancer

First-line therapy (squamous cell carcinoma only):

  • Administer 1 mg/kg intravenously every 6 weeks (given in combination with nivolumab every 2 or 3 weeks) until disease progression or unacceptable toxicity for up to 2 years

MSI-H/dMMR Esophageal and Esophagogastric/ Gastroesophageal Junction Cancer

First-line therapy, subsequent therapy, or induction therapy for relieving dysphagia:

  • Administer 1 mg/kg intravenously every 6 weeks for 16 weeks (given in combination with nivolumab every 2 weeks, then follow nivolumab monotherapy)

Neoadjuvant/perioperative therapy:

  • Administer 1 mg/kg intravenously every 6 weeks (given in combination with nivolumab every 2 weeks) for 12 weeks, followed by surgery and then postoperative therapy with nivolumab

Gastric Cancer

First-line therapy, subsequent therapy, or early-stage disease following endoscopic resection:

  • Administer 1 mg/kg intravenously every 6 weeks for 16 weeks (given in combination with nivolumab every 2 weeks, then follow nivolumab monotherapy)

Neoadjuvant/perioperative therapy:

  • Administer 1 mg/kg intravenously every 6 weeks (given in combination with nivolumab every 2 weeks) for 12 weeks, followed by surgery and then postoperative therapy with nivolumab

Hepatocellular Carcinoma (HCC)

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

Pleural Mesothelioma (PM) & Peritoneal Mesothelioma (PeM)

(including pericardial mesothelioma and tunica vaginalis testis mesothelioma)

Initial therapy:

  • Administer 1 mg/kg intravenously every 6 weeks (given in combination with nivolumab every 2 or 3 weeks) until disease progression or unacceptable toxicity for up to 2 years

Subsequent therapy:

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

Cutaneous Melanoma

Single agent or in combination with nivolumab as first-line or subsequent therapy:

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

In combination with nivolumab as neoadjuvant therapy:

  • Administer 1 mg/kg intravenously every 3 weeks for a maximum of 2 doses (given in combination with nivolumab on the same day)

Single agent as adjuvant therapy:

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

In combination with nivolumab as adjuvant therapy:

  • Administer 3 mg/kg intravenously every 3 weeks for a maximum of 4 doses (given in combination with nivolumab on the same day)

Uveal Melanoma

Single agent:

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

In combination with nivolumab:

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

Merkel Cell Carcinoma

Single agent or in combination with nivolumab:

  • Administer 1 mg/kg intravenously every 6 weeks (may be given in combination with nivolumab every 2 weeks) until disease progression or unacceptable toxicity

OR

  • Administer 3 mg/kg intravenously every 3 weeks for a maximum of 4 doses (when given with nivolumab every 3 weeks, may 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 3 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 histology-based platinum-doublet chemotherapy every 3 weeks for 2 cycles) until disease progression or unacceptable toxicity for up to 2 years

Soft Tissue Sarcoma

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

* All treatments given for a maximum of 4 doses must be administered within 16 weeks of the first dose.
  1. Billing Code/Availability Information

HCPCS Code:

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

NDC(s):

  • Yervoy 50 mg/10 mL injection single-dose vial: 00003-2327-xx
  • Yervoy 200 mg/40 mL injection single-dose vial: 00003-2328-xx
  1. References
  1. Yervoy [package insert]. Princeton, NJ; Bristol Meyers Squib; February 2023. Accessed June 2024.
  2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) ipilimumab. National Comprehensive Cancer Network, 2024. 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 2024.
  3. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Small Cell Lung Cancer. Version 3.2024. National Comprehensive Cancer Network, 2024. 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 June 2024.
  4. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Central Nervous System Cancers. Version 1.2024. National Comprehensive Cancer Network, 2024. 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 June 2024.
  5. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Mesothelioma: Pleural. Version 1.2024. National Comprehensive Cancer Network, 2024. 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 June 2024.
  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.
  1. Fahrenbruch R, Kintzel P, Bott AM, et al. Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology/Oncology Pharmacy Association. J Oncol Pract. 2018 Mar;14(3):e130-e136.
  2. Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from http://www.hoparx.org/images/hopa/advocacy/Issue-Briefs/Drug_Waste_2019.pdf
  3. Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.
  4. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Non-Small Cell Lung Cancer. Version 6.2024. National Comprehensive Cancer Network, 2024. 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 June 2024.
  1. Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015 May;16(5):522-30. doi: 10.1016/S1470-2045(15)70122-1. Epub 2015 Mar 31.
  2. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.
  3. 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 Mar 10;36(8):773-779. doi: 10.1200/JCO.2017.76.9901. Epub 2018 Jan 20.
  4. Piulats JM, Cruz-Merino LDL, Garcia MTC, et al. Phase II multicenter, single arm, open label study of nivolumab in combination with ipilimumab in untreated patients with metastatic uveal melanoma (GEM1402.NCT02626962). Annals of Oncology, Volume 29, Issue suppl_8, October 2018, mdy289.003, https://doi.org/10.1093/annonc/mdy289.003.
  5. Zimmer L, Vaubel J, Mohr P, et al. Phase II DeCOG-study of ipilimumab in pretreated and treatment-naïve patients with metastatic uveal melanoma. PLoS One. 2015 Mar 11;10(3):e0118564. doi: 10.1371/journal.pone.0118564. eCollection 2015.
  6. Danielli R, Ridolfi R, Chiarion-Sileni V, et al. Ipilimumab in pretreated patients with metastatic uveal melanoma: safety and clinical efficacy. Cancer Immunol Immunother. 2012 Jan;61(1):41-8. doi: 10.1007/s00262-011-1089-0. Epub 2011 Aug 11.
  1. Luke JJ, Callahan MK, Postow MA, et al. Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience. Cancer. 2013 Oct 15;119(20):3687-95. doi: 10.1002/cncr.28282. Epub 2013 Aug 2.
  2. Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2019 Nov 21;381(21):2020-2031. doi: 10.1056/NEJMoa1910231. Epub 2019 Sep 28.
  3. 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 Feb;20(2):239-253. doi: 10.1016/S1470-2045(18)30765-4. Epub 2019 Jan 16.
  4. Disselhorst MJ, Quispel-Janssen J, Lalezari F, et al. Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Lancet Respir Med. 2019 Mar;7(3):260-270. doi: 10.1016/S2213-2600(18)30420-X. Epub 2019 Jan 16.
  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.
  6. 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. doi: 10.1016/S1470-2045(12)70090-6. Epub 2012 Mar 27.
  7. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Small Bowel Adenocarcinoma. Version 3.2024. National Comprehensive Cancer Network, 2024. 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 June 2024.
  8. El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.
  9. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Colon Cancer. Version 3.2024. National Comprehensive Cancer Network, 2024. 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 June 2024.
  10. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Melanoma: Uveal. Version 1.2024. National Comprehensive Cancer Network, 2024. 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 June 2024.
  11. Hellmann M, Ott PA, Zugazagoitia J, et al. Nivolumab (nivo) ± ipilimumab (ipi) in advanced small-cell lung cancer (SCLC): First report of a randomized expansion cohort from CheckMate 032. J Clin Oncol 2017; 35 Abstract 8503.
  12. Zalcman G, Mazieres J, Greillier L, et al. Second- or third-line nivolumab (Nivo) versus nivo plus ipilimumab (Ipi) in malignant pleural mesothelioma (MPM) patients: Updated results of the IFCT-1501 MAPS2 randomized phase 2 trial [abstract]. Ann Oncol 2017; 28:Abstract LBA58_PR.
  13. Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2019;381(21):2020-2031. doi:10.1056/NEJMoa1910231.
  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.
  15. Zalcman G, Peters S, Mansfield AS, et al. Checkmate 743: A phase 3, randomized, open-label trial of nivolumab (nivo) plus ipilimumab (ipi) vs pemetrexed plus cisplatin or carboplatin as first-line therapy in unresectable pleural mesothelioma. Journal of Clinical Oncology 2017 35:15_suppl, TPS8581-TPS8581.
  16. Olson D, Luke J, Poklepovic A, et al. Significant antitumor activity for low-dose ipilimumab (IPI) with pembrolizumab (PEMBRO) immediately following progression on PD1 Ab in melanoma (MEL) in a phase II trial. Journal of Clinical Oncology 2020 38:15_suppl, 10004-10004
  17. Pelster MS, Gruschkus SK, Bassett R, et al. Nivolumab and Ipilimumab in Metastatic Uveal Melanoma: Results From a Single-Arm Phase II Study. J Clin Oncol. 2021 Feb 20;39(6):599-607. doi: 10.1200/JCO.20.00605.
  18. Carlino MS, Menzies AM, Atkinson V, et al. Long-term Follow-up of Standard-Dose Pembrolizumab Plus Reduced-Dose Ipilimumab in Patients with Advanced Melanoma: KEYNOTE-029 Part 1B. Clin Cancer Res. 2020 Oct 1;26(19):5086-5091. doi: 10.1158/1078-0432.CCR-20-0177.
  19. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015 Jul 2;373(1):23-34. doi: 10.1056/NEJMoa1504030. Epub 2015 May 31.
  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.
  3. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Mesothelioma: Peritoneal. Version 1.2024. National Comprehensive Cancer Network, 2024. 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 June 2024.
  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.
  5. Schenker M, Burotto M, Richardet M, et al. CheckMate 848: A randomized, open-label, phase 2 study of nivolumab in combination with ipilimumab or nivolumab monotherapy in patients with advanced or metastatic solid tumors of high tumor mutational burden. Oral Presentation presented at the American Association for Cancer Research (AACR) 2022 Annual Meeting; April 8-13, 2022; New Orleans, LA.
  6. Zer A, Icht O, Yosef L, et al. Phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (cKS). Annals of Oncology. Volume 33, Issue 7, July 2022, Pages 720-727. https://doi.org/10.1016/j.annonc.2022.03.012.
  7. Blank CU, Rozeman EA, Fanchi LF, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat Med. 2018 Nov;24(11):1655-1661. doi: 10.1038/s41591-018-0198-0.
  8. Baas P, Scherpereel A, Nowak AK, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021 Jan 30;397(10272):375-386. doi: 10.1016/S0140-6736(20)32714-8.
  9. Glutsch V, Kneitz, Gesierich A, et al. Activity of ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma. Cancer Immunology, Immunotherapy volume 70, pages2087–2093 (2021).
  10. Kim S, Wuthrick E, Blakaj D, et al. Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomized, open label, phase 2 trial. The Lancet. Published: September 11, 2022. doi:https://doi.org/10.1016/S0140-6736(22)01659-2. PlumX Metrics.
  11. Wagner M, Othus M, Patel S, et al. Multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART). J Immunother Cancer. 2021 Aug;9(8):e002990. doi: 10.1136/jitc-2021-002990.
  12. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Esophageal and Esophagogastric Junction Cancers. Version 3.2024. National Comprehensive Cancer Network, 2024. 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 June 2024.
  13. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Gastric Cancer. Version 2.2024. National Comprehensive Cancer Network, 2024. 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 June 2024.
  14. LoPiccolo J, Schollenberger MD, Dakhil S, et al. Rescue therapy for patients with anti-PD-1-refractory Merkel cell carcinoma: a multicenter, retrospective case series. J Immunother Cancer. 2019 Jul 8;7(1):170. doi: 10.1186/s40425-019-0661-6.
  15. Dagogo-Jack I, Madison RW, Lennerz JK, et al. Molecular characterization of mesothelioma: Impact of histologic type and site of origin on molecular landscape. JCO Precis Oncol 2022;6:e2100422.
  16. Yau T, Kang YK, Kim TY, et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: The CheckMate 040 randomized clinical trial. JAMA Oncol 2020;6:e204564.
  17. Reijers ILM, Menzies AM, van Akkooi ACJ, et al. Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma: the PRADO trial. Nat Med 2022;28:1178-1188.
  18. Versluis JM, Menzies AM, Sikorska K, et al. Survival update of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma in the OpACIN and OpACINneo trials. Ann Oncol 2023;34:420-430.
  19. Referenced with permission from the NCCN Clinical Practice Guidelines (NCCN Guidelines®) Melanoma: Cutaneous Version 2.2024. National Comprehensive Cancer Network, 2024. 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 June 2024.

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

C16.1

Malignant neoplasm of fundus of stomach

C16.2

Malignant neoplasm of body of stomach

C16.3

Malignant neoplasm of pyloric antrum

C16.4

Malignant neoplasm of pylorus

C16.5

Malignant neoplasm of lesser curvature of stomach, unspecified

C16.6

Malignant neoplasm of greater curvature of stomach, unspecified

C16.8

Malignant neoplasm of overlapping sites of stomach

C16.9

Malignant neoplasm of stomach, unspecified

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

C22.1

Intrahepatic bile duct carcinoma

C22.3

Angiosarcoma of liver

C22.8

Malignant neoplasm of liver, primary, unspecified as to type

C22.9

Malignant neoplasm of liver, not specified as primary or secondary

C23

Malignant neoplasm of gallbladder

C24.0

Malignant neoplasm of extrahepatic bile duct

C24.1

Malignant neoplasm of ampulla of Vater

C24.8

Malignant neoplasm of overlapping sites of biliary tract

C24.9

Malignant neoplasm of biliary tract, unspecified

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

C40.00

Malignant neoplasm of scapula and long bones of unspecified upper limb

C40.01

Malignant neoplasm of scapula and long bones of right upper limb

C40.02

Malignant neoplasm of scapula and long bones of left upper limb

C40.10

Malignant neoplasm of short bones of unspecified upper limb

C40.11

Malignant neoplasm of short bones of right upper limb

C40.12

Malignant neoplasm of short bones of left upper limb

C40.20

Malignant neoplasm of long bones of unspecified lower limb

C40.21

Malignant neoplasm of long bones of right lower limb

C40.22

Malignant neoplasm of long bones of left lower limb

C40.30

Malignant neoplasm of short bones of unspecified lower limb

C40.31

Malignant neoplasm of short bones of right lower limb

C40.32

Malignant neoplasm of short bones of left lower limb

C40.80

Malignant neoplasm of overlapping sites of bone and articular cartilage of unspecified limb

C40.81

Malignant neoplasm of overlapping sites of bone and articular cartilage of right limb

C40.82

Malignant neoplasm of overlapping sites of bone and articular cartilage of left limb

C40.90

Malignant neoplasm of unspecified bones and articular cartilage of unspecified limb

C40.91

Malignant neoplasm of unspecified bones and articular cartilage of right limb

C40.92

Malignant neoplasm of unspecified bones and articular cartilage of left limb

C41.0

Malignant neoplasm of bones of skull and face

C41.1

Malignant neoplasm of  mandible

C41.2

Malignant neoplasm of vertebral column

C41.3

Malignant neoplasm of ribs, sternum and clavicle

C41.4

Malignant neoplasm of pelvic bones, sacrum and coccyx

C41.9

Malignant neoplasm of bone and articular cartilage, unspecified

C43.0

Malignant melanoma of lip

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

C46.0

Kaposi's sarcoma of skin

C46.1

Kaposi's sarcoma of soft tissue

C46.2

Kaposi's sarcoma of palate

C46.3

Kaposi's sarcoma of lymph nodes

C46.4

Kaposi's sarcoma of gastrointestinal sites

C46.50

Kaposi's sarcoma of unspecified lung

C46.51

Kaposi's sarcoma of right lung

C46.52

Kaposi's sarcoma of left lung

C46.7

Kaposi's sarcoma of other sites

C46.9

Kaposi's sarcoma, unspecified

C47.0

Malignant neoplasm of peripheral nerves of head, face and neck

C47.10

Malignant neoplasm of peripheral nerves of unspecified upper limb, including shoulder

C47.11

Malignant neoplasm of peripheral nerves of right upper limb, including shoulder

C47.12

Malignant neoplasm of peripheral nerves of left upper limb, including shoulder

C47.20

Malignant neoplasm of peripheral nerves of unspecified lower limb, including hip

C47.21

Malignant neoplasm of peripheral nerves of right lower limb, including hip

C47.22

Malignant neoplasm of peripheral nerves of left lower limb, including hip

C47.3

Malignant neoplasm of peripheral nerves of thorax

C47.4

Malignant neoplasm of peripheral nerves of abdomen

C47.5

Malignant neoplasm of peripheral nerves of pelvis

C47.6

Malignant neoplasm of peripheral nerves of trunk, unspecified

C47.8

Malignant neoplasm of overlapping sites of peripheral nerves and autonomic nervous system

C47.9

Malignant neoplasm of peripheral nerves and autonomic nervous system, unspecified

C48.0

Malignant neoplasm of retroperitoneum

C48.1

Malignant neoplasm of specified parts of peritoneum

C48.2

Malignant neoplasm of peritoneum, unspecified

C48.8

Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum

C49.0

Malignant neoplasm of connective and soft tissue of head, face and neck

C49.10

Malignant neoplasm of connective and soft tissue of unspecified upper limb, including shoulder

C49.11

Malignant neoplasm of connective and soft tissue of right upper limb, including shoulder

C49.12

Malignant neoplasm of connective and soft tissue of left upper limb, including shoulder

C49.20

Malignant neoplasm of connective and soft tissue of unspecified lower limb, including hip

C49.21

Malignant neoplasm of connective and soft tissue of right lower limb, including hip

C49.22

Malignant neoplasm of connective and soft tissue of left lower limb, including hip

C49.3

Malignant neoplasm of connective and soft tissue of thorax

C49.4

Malignant neoplasm of connective and soft tissue of abdomen

C49.5

Malignant neoplasm of connective and soft tissue of pelvis

C49.6

Malignant neoplasm of connective and soft tissue of trunk, unspecified

C49.8

Malignant neoplasm of overlapping sites of connective and soft tissue

C49.9

Malignant neoplasm of connective and soft tissue, unspecified

C4A.0

Merkel cell carcinoma of lip

C4A.10

Merkel cell carcinoma of eyelid, including canthus

C4A.111

Merkel cell carcinoma of right upper eyelid, including canthus

C4A.112

Merkel cell carcinoma of right lower eyelid, including canthus

C4A.121

Merkel cell carcinoma of left upper eyelid, including canthus

C4A.122

Merkel cell carcinoma of left lower eyelid, including canthus

C4A.20

Merkel cell carcinoma of unspecified ear and external auricular canal

C4A.21

Merkel cell carcinoma of right ear and external auricular canal

C4A.22

Merkel cell carcinoma of left ear and external auricular canal

C4A.30

Merkel cell carcinoma of unspecified part of face

C4A.31

Merkel cell carcinoma of nose

C4A.39

Merkel cell carcinoma of other parts of face

C4A.4

Merkel cell carcinoma of scalp and neck

C4A.51

Merkel cell carcinoma of anal skin

C4A.52

Merkel cell carcinoma of skin of breast

C4A.59

Merkel cell carcinoma of other part of trunk

C4A.60

Merkel cell carcinoma of unspecified upper limb, including shoulder

C4A.61

Merkel cell carcinoma of right upper limb, including shoulder

C4A.62

Merkel cell carcinoma of left upper limb, including shoulder

C4A.70

Merkel cell carcinoma of unspecified lower limb, including hip

C4A.71

Merkel cell carcinoma of right lower limb, including hip

C4A.72

Merkel cell carcinoma of left lower limb, including hip

C4A.8

Merkel cell carcinoma of overlapping sites

C4A.9

Merkel cell carcinoma, 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

C72.0

Malignant neoplasm of spinal cord

C72.1

Malignant neoplasm of cauda equina

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

C7B.1

Secondary Merkel cell carcinoma

D37.1

Neoplasm of uncertain behavior of stomach

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

Z85.028

Personal history of other malignant neoplasm of stomach

Z85.068

Personal history of other malignant neoplasm of small intestine

Z85.09            Personal history of malignant neoplasm of other digestive organs

Personal history of malignant neoplasm of other digestive organs

Z85.118

Personal history of other malignant neoplasm of bronchus and lung

Z85.820

Personal history of malignant melanoma of skin

Z85.821

Personal history of Merkel cell carcinoma

Z85.830

Personal history of malignant neoplasm of bone

Z85.831

Personal history of malignant neoplasm of soft tissue

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

The preceding information is intended for non-Medicare coverage determinations. 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 Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied 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

M (11)

NC, SC, WV, VA (excluding below)

Palmetto GBA

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

 

 

 


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