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Asset Publisher
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. |
- 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.
- Dosing Limits
- 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)
- 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 |
- 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
- Used as subsequent treatment for progression on or after systemic treatment for unresectable, resected gross residual (R2), or metastatic disease; AND
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
- Patient has squamous cell carcinoma †; AND
- 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
- Used as first-line therapy; AND
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
- Used as first-line or subsequent therapy; AND
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 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 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 a single agent; AND
- 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
- Patient stage III disease; AND
- Used in combination with nivolumab; AND
*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 for one of the following:
- 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 for one of the following:
- 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
- Used as first-line therapy; AND
** 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 |
|
|
|
|
ALK rearrangement-positive tumors |
ROS1 rearrangement-positive tumors |
BRAF V600E-mutation positive tumors |
ERBB2 (HER2) mutation positive tumors |
|
|
|
|
PD-L1 tumor expression ≥ 1% |
MET exon-14 skipping mutations |
RET rearrangement-positive tumors |
KRAS G12C mutation positive tumors |
|
|
|
|
- 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:
|
- 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:
In combination with nivolumab:
|
Colorectal Cancer (CRC) |
Neoadjuvant therapy
Primary/initial treatment
Subsequent therapy
|
Appendiceal Adenocarcinoma |
Primary/initial treatment
Subsequent therapy
|
Esophageal and Esophagogastric/ Gastroesophageal Junction Cancer |
First-line therapy (squamous cell carcinoma only):
|
MSI-H/dMMR Esophageal and Esophagogastric/ Gastroesophageal Junction Cancer |
First-line therapy, subsequent therapy, or induction therapy for relieving dysphagia:
Neoadjuvant/perioperative therapy:
|
Gastric Cancer |
First-line therapy, subsequent therapy, or early-stage disease following endoscopic resection:
Neoadjuvant/perioperative therapy:
|
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:
Subsequent therapy:
|
Cutaneous Melanoma
|
Single agent or in combination with nivolumab as first-line or subsequent therapy:
In combination with pembrolizumab as subsequent therapy:
In combination with nivolumab as neoadjuvant therapy:
Single agent as adjuvant therapy:
In combination with nivolumab as adjuvant therapy:
|
Uveal Melanoma |
Single agent:
In combination with nivolumab:
|
Merkel Cell Carcinoma |
Single agent or in combination with nivolumab:
OR
|
Non-Small Cell Lung Cancer (NSCLC) |
In combination with nivolumab:
In combination with nivolumab and platinum-doublet chemotherapy:
|
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. |
- 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
- References
- Yervoy [package insert]. Princeton, NJ; Bristol Meyers Squib; February 2023. Accessed June 2024.
- 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.
- 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.
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- 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.
- 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
- 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.
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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 |