The efficacy of Poteligeo was established in Study 0761-010, a randomized, open-label, multicenter trial of 372 adult patients with MF or SS after at least one prior systemic therapy. Patients are randomized 1:1 to receive either Poteligeo (186 patients; 56% with MF, 44% with SS) or vorinostat (186 patients; 53% with MF, 47% with SS). The dose of Poteligeo was 1 mg/kg administered intravenously over at least 60 minutes on days 1, 8, 15, and 22 of the first 28-day cycle and on days 1 and 15 of each subsequent cycle. Vorinostat was dosed at 400 mg orally once daily, continuously for 28-day cycles. Treatment continued until disease progression or unacceptable toxicity. Vorinostat-treated patients with disease progression or unacceptable toxicities were permitted to cross over to Poteligeo.

Efficacy was based on investigator-assessed progression-free survival (PFS), overall response rate (ORR) based on global composite response criteria that combine measures from each disease compartment (skin, blood, lymph nodes and viscera). The trial demonstrated that Poteligeo significantly prolonged PFS compared to vorinostat . The estimated median PFS was 7.7 months in the Poteligeo arm and 3.1 months in the vorinostat arm (HR 0.53, p<0.001). Median PFS was 6.7 months (95%CI,5.6, 9.4) for Poteligeo and 3.8 months (95%CI, 3.0, 4.7) for vorinostat with disease progression assessed by blinded independent review (HR 0.64l 95%CI, 0.49, 0.84; p<0.0007). The ORR is 28% in Poteligeo group and 5% in vorinostat group (p<0.001). Median duration of overall response is 13.9 months in Poteligeo group and 9.0 months in vorinostat group.

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)

1. Mogamulizumab-kpkc (Poteligeo) is medically necessary for the following FDA approved indications when ALL of the following criteria are met:
• For the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) (documentation of medical records required)
  • The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient’s diagnosis
  • Members ≥ 18 years of age
  • To be used as a single systemic agent
  • Failure of at least one prior course of systemic therapy (documentation of medical records required), including extracorporeal photopheresis (ECP) retinoids (bexarotene, all-trans retinoic acidm isotretinoin), interferons (IFN-alpha, IFN-gamma), HDAC-inhibitors (vorinostat, romidepsin), methotrexate, brentuximab vedotin, doxorubicin, gemcitabine, etoposide, chlorambucil, pentosatin, cyclophosphamide, temozolomide, bortezomib, pembrolizumab or low dose pralatrexate. Psoralen plus ultraviolet light therapy (PUVA) is not considered to be a systemic therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1
  • Members with a known history of non-complicated staphylococcus infection/colonization must continue to receive stable doses of prophylactic antibiotics
  • Women of childbearing potential (WOCBP) must have a negative pregnancy test prior to therapy initiation. Member and their partners of childbearing potential must agree to use effective contraception throughout treatment duration and for 3 months after the last dose of Poteligeo
  • Member does not have any of the following:
    • Prior allogeneic hematopoietic stem cell transplant (HSCT) or autologous HSCT within the last 90 days
    • Clinical evidence of central nervous system (CNS) metastasis
    • Known or tests positive for human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV-1), hepatitis B or hepatitis C
    • Active herpes simplex or herpes zoster. (Members on prophylaxis for herpes who started taking medication at least 30 days prior to therapy initiation, and have no active signs of active infection, and whose last active infection was more than 6 months ago, may be eligible, and should continue to take the prescribed medication for the duration of treatment)
    • Known active autoimmune disease (i.e. Grave's disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease; psoriasis, etc.)

	T/N/M/B	TNMB Classification and Staging of Mycosis Fungoides and Sezary Syndrome
Skin	T1 T2 T2a T2b T3 T4	Limited patches, pupules, and/or plaques covering <10% of the skin surface Patches, papules, and/or plaques covering ≥ 10% of the skin surface Patch only Plaque ± patch One or more tumors (≥1cm in diameter) Confluence of erythema ≥80% body surface area
Node	N0 N1 N2 N3 NX	No abnormal lymph nodes; biopsy not required Abnormal lymph nodes; histopathology Dutch Gr 1 or NCI LN 0-2 Abnormal lymph nodes; histopathology Dutch Gr 2 or NCI LN 3 Abnormal lymph nodes; histopathology Dutch Gr 3-4 or NCI LN 4 Abnormal lymph nodes; no histologic confirmation
Visceral	M0 M1 MX	No visceral organ involvement Visceral involvement (must have pathology confirmation and organ involved should be specified) Abnormal visceral site; no histologic confirmation
Blood	B0 B1 B2	Absence of significant blood involvement ≤5% of peripheral blood lymphocytes or <250mcL are atypical (Sezary) cells or <15% CD4+/CD26- or CD4+/CD7 cells of total lymphocytes Low blood tumor burden: >5% of peripheral blood lymphocytes are atypical (Sezary) cells or ≥15% CD4+CD26- or CD4+CD7- of total lymphocytes but do not meet the criteria of B0 or B2 High blood tumor burden: ≥1000/mcL Sezary cells (CD4+/CD26- or CD4+/CD7- cells by flow cytometry) or CD4/CD8≥10 or ≥40% CD4+/CD7- or ≥30%CD4+/CD26- cells of total lymphocytes

	T	N	M	B
IA IB	1 2	0 0	0 0	0,1 0,1
IIA IIB	1-2 3	1.2 0-2	0 0	0,1 0,1
IIIA IIIB	4 4	0-2 0-2	0 0	0 1
IVA1 IVA2 IVB	1-4 1-4 1-4	0-2 3 0-3	0 0 1	2 0-2 0-2

2. When mogamulizumab-kpkc (Poteligeo) is medically necessary, initial therapy will be approved for 6 months at the FDA recommended dosage of:
• Relapsed or refractory mycosis fungoides (MF) or Sézary syndrome
  • 1 mg/kg as an intravenous infusion over at least 60 minutes on days 1, 8, 15, and 22 of the first 28-day cycle and on days 1 and 15 of each subsequent 28-day cycle
[INFORMATIONAL NOTE: As per the FDA approved package insert
• Pre-medicate with diphenhydramine and acetaminophen for the first Poteligeo infusion
• Permanently discontinue Poteligeo for life-threatening (Grade 4) rash or for any Sevens-Johnson syndrome (SJ) or toxic epidermal necrolysis (TEN). If SJS or TEN is suspected, stop Poteligeo and do not resume unless SJS or TEN has been excluded and the cutaneous reaction has resolved to Grade 1 or less.
• If moderate or severe (Grade 2 or 3) rash occurs, interrupt Poteligeo and administer at least 2weeks of topical corticosteroids.
• If mild (Grade 1) rash occurs, consider topical corticosteroids]

3. Mogamulizumab-kpkc (Poteligeo) is medically necessary for annual approval if the patient meets the following criteria:
• Tumor response with stabilization of disease or decrease in size of tumor or tumor spread, AND
• Absence of unacceptable toxicity, including dermatologic toxicity (SJS, TEN), severe infection (sepsis), or life-threatening immune-mediated complications (hepatitis, myocarditis, myositis, etc.)
4. Mogamulizumab-kpkc (Poteligeo) is considered medically necessary for “off-label” ndications that have in effect a rating of 'Category 1' or 'Category 2A' in the current recommendations in the National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - mogamulizumab-kpkc. Available at: [https://www.nccn.org/professionals/drug_compendium/content/]

5. Other uses of mogamulizumab-kpkc (Poteligeo) are considered investigational.

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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Mogamulizumab-kpkc (Poteligeo)
Poteligeo (Mogamulizumab-kpkc)

References:
1. Kyowa Kirin. Poteligeo Package Insert. Bedminster Township, NJ. August 2018.

2. Mogamulizumab-kpkc. Clinicaltrial.gov. Accessed on 8/25/18. Available at: https://clinicaltrials.gov/ct2/show/NCT01728805

3. Mogamulizumab (Poteligeo). Micromedex. DrugDex Evaluations. Updated 12/6/19. Accessed at http://www.micromedexsolutions.com/micromedex2. Accessed July 30, 2020.

4. National Comprehensive Cancer Network (NCC) Drugs and Biologics Compendium. 2020. Available at https://www.nccn.org/professionals/drug_compendium/content/. Accessed: July 30, 2020.

5. National Comprehensive Cancer Network (NCCN) Guidelines. 2019. Available at https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf. Accessed: May 17, 2019.

6. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55.