Effective Date:

a)    This policy will apply to all services performed on or after the above revision date which will become the new effective date.

b)    For all services referred to in this policy that were performed before the revision date, contact customer service for the rules that would apply.

1)    Yervoy (Ipilimumab) requires prior authorization.

2)    Yervoy (Ipilimumab) is used to treat unresectable or metastatic malignant melanoma, advanced renal-cell cancer, metastatic colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer, esophageal cancer and malignant pleural mesothelioma.

Yervoy (ipilimumab) is considered medically necessary when the following criteria are met:

I.             Initial Approval Criteria

a.    Melanoma (must meet all):

                                          i.    Diagnosis if unresectable, metastatic, or lymph node positive melanoma;

                                        ii.    Prescribed by or in consultation with an oncologist;

                                       iii.    Age is one of the following:

1.    For unresectable or metastatic disease: > 12 years;

2.    For adjuvant treatment: > 18 years

                                       iv.    Prescribed in one of the following ways:

1.    As a single agent;

2.    In combination with Opdivo for unresectable or metastatic melanoma;

3.    In combination with Keytruda for unresectable or metastatic melanoma;

Approval duration: 6 months

b.    Renal Cell Carcinoma (must meet all):

                                          i.    Diagnosis of advanced or metastatic RCC

                                        ii.    Prescribed by or in consultation with an oncologist;

                                       iii.    Age > 12 years;

                                       iv.    Prescribed in combination with Opdivo;

Approval duration: 16 weeks (maximum of 4 doses)

c.    Colorectal Cancer (must meet al):

                                          i.    Diagnosis of MSI-H or dMMR CRC;

                                        ii.    Prescribed by or in consultation with an oncologist;

                                      iii.    Age > 12 years;

                                       iv.    Disease is unresectable or metastatic

                                        v.    Prescribed in combination with Opdivo;

Approval duration: 16 weeks (maximum of 4 doses)

d.    Hepatocellular Carcinoma (must meet all):

                                         i.    Diagnosis of HCC;

                                        ii.    Prescribed by or in consultation with an oncologist;

                                       iii.    Age > 18 years;

                                       iv.    Member has previously received Nexavar, Lenvima, or Tecentriq + bevacizumab or Imfinzi;

                                        v.    Prescribed in combination with Opdivo;

                                       vi.    Documentation of Child Pugh Class A status;

Approval Duration 16 weeks (maximum 4 doses)

e.    Non-Smnall Cell Lung Cancer (must meet all):

                                         i.    Diagnosis of recurrent, advanced, or metastatic NSCLC;

                                        ii.    Prescribed by or in consultation with an oncologist;

                                      iii.    Age > 18 years;

                                      iv.    Prescribed in combination with Opdivo;

                                        v.    Member does not have contraindications to PD-1/PD-L1 inhibitor therapy (e.g., Opdivo, Keytruda, Tecentriq, Imfibnzi);

                                       vi.    Requests meets one of the following:

1.    Disease mutation status is negative for actionable biomarkers (EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET and ERBB2 [HER2]), and member has not received prior systemic therapy for advanced disease;

2.    Disease mutation status is positive for EGFR S768I, L861Q, and/or G719X, and member has received prior afatinib, osimertinib, erlotinib, gefitinib, or dacomitinib;*

3.    Disease mutation status is positive for EGFR exon 19 deletion or L858R, and member has received prior erlotinib ± (ramucirumab or bevacizumab), afatinib, gefitinib, osimertinib, or dacomitinib;*

4.    Disease mutation status is positive for ROS1 rearrangement, and member has received prior crizotinib, entrectinib, or ceritinib;*

5.    Disease mutation status is positive for ALK rearrangement, and member has received prior crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib;* f. Disease mutation status is positive for EGFR exon 20, KRAS G12C, NRTK1/2/3, BRAF V600E, MET exon 14 skipping, RET rearrangement, or ERBB2 (HER2);

Approval Duration: 6 months

f.     Malignant Pleural Mesothelioma (must meet all):

                                         i.    Diagnosis of unresectable malignant pleural mesothelioma;

                                        ii.    Prescribed by or in consultation with an oncologist;

                                      iii.    Age > 18 years;

                                      iv.    Prescribed in combination with Opdivo;

Approval Duration: 6 months

g.    Esophageal Cancer (must meet all):

                                         i.    Diagnosis of unresectable advanced or metastatic ESCC;

                                        ii.    Prescribed by or in consultation with an oncologist;

                                      iii.    Age >18 years;

                                      iv.    Prescribed in combination with Opdivo;

Approval Duration: 6 months

h.    NCCN Compendium Indications (off-label) (must meet all):

                                          i.    Diagnosis of one of the following (a-f):

1.    MSI-H or dMMR small bowel adenocarcinoma;

2.    Metastatic uveal melanoma;

3.    MSI-H or dMMR ampullary adenocarcinoma;

4.    Bone cancer (e.g., chondrosarcoma, osteosarcoma, chordoma, Ewing sarcoma), and both of the following:

a.    Disease is unresectable or metastatic with tissue tumor mutation burden-high tumors with 10 or more mutations per megabase;

b.    Disease has progressed following prior treatment and no satisfactory alternative treatment options exist; e. BRAF non-specific melanoma brain metastases; f. Classic Kaposi sarcoma as subsequent systemic therapy;

                                        ii.    Prescribed by or in consultation with an oncologist;

                                       iii.    Age ≥ 12 years;

                                       iv.     Prescribed in combination with Opdivo for all of the following (a-d):* a. MSI-H/dMMR small bowel adenocarcinoma;

b. MSI-H/dMMR ampullary adenocarcinoma;

c. Bone cancer; d. Classic Kaposi sarcoma;

v. For uveal melanoma or brain metastases: Prescribed as a single agent or in combination with Opdivo;* *Prior authorization may be required for Opdivo

vi. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).* *Prescribed regimen must be FDA-approved or recommended by NCCN

            Approval Duration: 6 months

II.            Continued Therapy

a.    Melanoma - Unresectable or Metastatic

                                          i.    Reauthorization beyond 16 weeks is not permitted. Members must meet the initial approval criteria, at a minimum of 3 months since initial treatment discontinuation.

Approval duration: Not applicable

                                        ii.    Renal Cell Carcinoma, Colorectal Cancer, Hepatocellular Carcinoma

1.    Reauthorization beyond 16 weeks is not permitted. Members must meet the initial approval criteria.

Approval duration: Not applicable

                                       iii.    Melanoma (Adjuvant Treatment), Non-Small Cell Lung Cancer, Malignant Pleural Mesothelioma, Esophageal Cancer (must meet all):

1.    Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Yervoy and has received this medication for at least 30 days;

2.    Member is responding positively to therapy;

3.    If request is for a dose increase, request meets one of the following (a, b, or c):*

a. For melanoma: New dose does not exceed 10 mg/kg every 12 weeks for up to 3 years;

b. For NSCLC, malignant pleural mesothelioma, and ESCC: New dose does not exceed 1 mg/kg IV every 6 weeks in combination with Opdivo;

c. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

*Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: 12 months or up to a total duration of 3 years (cutaneous melanoma) or 2 years (NSCLC, malignant pleural mesothelioma, ESCC), whichever is less.

Codes Used In This BI:

J9228    Ipilimumab Injection, 1mg

1)    Yervoy Product Information.  Bristol-Myers Squibb.  March 2023.

2)    NCCN Drug Compendium Guidelines.  Accessed online Aopril 12, 2023

3)    National Comprehensive Cancer Network. Malignant Pleural Mesothelioma Version 1.2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/mpm.pdf. Accessed February 7, 2023.

4)    National Comprehensive Cancer Network. Non-Small Cell Lung Cancer Version 1.2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed February 7, 2023.

5)    Hellman MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019 November; 381(21):2020-2031.

6)    National Comprehensive Cancer Network. Hepatobiliary Cancers, Version 5.2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. Accessed February 7, 2023.

7)    National Comprehensive Cancer Network. Esophageal and Esophagogastric Junction Cancers, Version 5.2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf. Accessed February 7, 2023.

8)    National Comprehensive Cancer Network. Melanoma:Cutaneous, Version 02.2023. Available at: www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf. Accessed April 12, 2023.

Addendum:

1)    Effective 01/01/2017: Removed HCPCS code C9284 from Claim Statement & Codes Used in This BI section. This code was deleted effective 1/1/12.

2)    Effective 02/01/2019: Added approved indications of advanced renal-cell cancer and metastatic colorectal cancer.

3)    Effective 06/01/2019: Added age range for metastatic melanoma and length of approval. Added covered indications of cutaneous melanoma, small cell lung cancer, and non-small cell lung cancer.

4)    Effective 11/01/2022: Updated to include coverage criteria for hepatocellular carcinoma, pleural mesothelioma, small bowel adenocarcinoma, and uveal melanoma.

5)    Effective 08/01/2023: Complete revision/update of criteria.