Notification



Notification Issue Date:



Policy Attachment


Attachment to Policy # 08.01.01i


Attachment:A

Policy #:08.01.01i

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

Title:Ipilimumab (Yervoy®)



DOSING AND FREQUENCY REQUIREMENTS FOR IPILIMUMAB (YERVOY®)

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

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


Indication
Dosing and Frequency
BRAIN METASTASES 1, 2, 4 Single:
Induction 10 mg/kg IV every 3 weeks for up to 4 doses
Maintenance 10 mg/kg IV every 12 weeks until disease progression or unacceptable toxicity

Combination:
Ipilimumab (IPI) + nivolumab (NIVO)

NIVO 1mg/kg IV and IPI 3mg/kg IV every 3 weeks for up to 4 doses;
followed by NIVO 240 mg IV every 2 weeks until disease progression or unacceptable toxicity

OR

NIVO 3mg/kg IV and IPI 1 mg/kg IV every 3 weeks for up to 4 doses;
followed by NIVO 3mg/kg IV every 2 weeks until disease progression or unacceptable toxicity
MELANOMA (METASTATIC OR UNRESECTABLE) 3, 4, 5, 6 3 mg/kg IV every 3 weeks for up to 4 doses. In the event of toxicity, doses may be delayed, but all treatment must be administered within 16 weeks of the first dose.
MELANOMA (ADJUVANT TREATMENT AFTER COMPLETE RESECTION) 5, 6Induction: 10 mg/kg IV every 3 weeks for 4 doses

Maintenance: 10 mg/kg IV every 12 weeks for up to 3 years or until disease progression or unacceptable toxicity
RENAL CELL CARINCOMA, ADVANCED 51 mg/kg IV every 3 weeks for up to 4 doses
SMALL CELL LUNG CANCER4, 63 mg/kg IV every 3 weeks for up to 4 doses
UVEAL MELANOMA7, 8Single: 3 mg/kg IV every 3 weeks for up to 4 doses

Combination:
Ipilimumab (IPI) + nivolumab (NIVO)

NIVO 1mg/kg IV and IPI 3mg/kg IV every 3 weeks for up to 4 doses;
followed by NIVO 3mg/kg IV every 2 weeks until disease progression or unacceptable toxicity.
MALIGNANT PLEURAL MESOTHELIOMA 9, 10 ,11,12Combination:
Ipilimumab (IPI)+ nivolumab (NIVO)

NIVO 3 mg/kg IV on Days 1, 15, and 29 and
IPI 1 mg/kg IV on Day 1;
every 6 weeks until disease progression or unacceptable toxicity for a maximum of 2 years

OR

NIVO 240 mg IV every 2 weeks until disease progression or unacceptable toxicity for a maximum of 2 years and
IPI 1 mg/kg IV every 6 weeks for up to 4 doses
COLORECTAL CANCER 13 14, 15 Combination:
Ipilimumab (IPI)+ nivolumab (NIVO)

NIVO 3 mg/kg IV and IPI 1 mg/kg IV
every 3 weeks for up to 4 doses;
followed by NIVO 3 mg/kg IV or NIVO 240 mg IV every 2 weeks until disease progression or unacceptable toxicity
SMALL BOWEL ADENOCARCINOMA 14, 16Combination:
Ipilimumab (IPI) + nivolumab (NIVO)

NIVO 3 mg/kg IV and IPI 1 mg/kg IV
every 3 weeks for up to 4 doses;
followed by NIVO 3 mg/kg IV or NIVO 240 mg IV every 2 weeks until disease progression or unacceptable toxicity
NON-SMALL CELL LUNG CANCER (NSCLC) 17, 18Combination:
Ipilimumab (IPI) + nivolumab (NIVO)

ipilimumab 1 mg/kg IV every 6 weeks and nivolumab 3 mg/kg IV every 2 weeks

platinum doublet chemotherapy based on tumor histologic type every 3 weeks for up to four cycles



REFERENCES:

1. Margolin K, Ernstoff MS, Hamid O, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13(5):459-65.

2. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 1.2019; CNS Cancers. [NCCN Website]. 03/05/2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. [via free subscription only]. Accessed March 08, 2019.

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

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

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

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

7. 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;10(3):e0118564.

8. Piulats JM, De La Cruz-Merino L, Curiel Garcia MT, et al. Phase II multicenter, single arm, open label study of nivolumab (NIVO) in combination with ipilimumab (IPI) as first line in adult patients (pts) with metastatic uveal melanoma (MUM). [American Society of 'clinical Oncology]. 05/20/2017. Available at: https://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.9533. Accessed Accessed March 08, 2019.

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

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

11. Zalcman G, Mazieres J, Greillier L, et al. Second or 3rd 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. [Oxford University Press Web site]. 09/05/2017. Available at: https://academic.oup.com/annonc/article/28/suppl_5/mdx440.074/4109986. Accessed March 08, 2019.

12. 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;7(3):260-270.

13 National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology- Colon Cancer. V4.2018. [NCCN Web site]. 10/19/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf [via subscription only]. Accessed March 08, 2019.

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

15. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology-Rectal Cancer. V3.2018. [NCCN Web site]. 08/07/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf [via subscription only]. Accessed March 08, 2019.

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

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


18. 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;17(7):883-895.




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

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