Lifileucel (Amtagvi) - Medical Clinical Policy Bulletins (2024)

Number:1056

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

Policy

Scope of Policy

This Clinical Policy Bulletin addresseslifileucel (Amtagvi) for commercial medical plans. For Medicare criteria, seeMedicare Part B Criteria.

Note: Requires Precertification:

Precertification of lifileucel (Amtagvi)is required of all Aetna participating providers and members in applicable plan designs. For precertification of lifileucel (Amtagvi),contact National Medical Excellence (NME) at 877-212-8811.

Note: Unless member's health plan has elected not to require, gene and cellular therapies must be administered at an Aetna Institutes® Gene Based, Cellular and Other Innovative Therapy (GCIT®) Network. For lifileucel (Amtagvi), see Aetna Institutes® GCIT Designated Centers.

1. Criteria for Initial Approval

   Melanoma

   Aetna considers lifileucel (Amtagvi) medically necessary for the treatment of unresectable or metastatic melanoma in members 18 years and older when all of the following criteria are met:

   1. The member has received prior treatment with the following drug categories:

      1. PD-1 blocking antibody (e.g., Keytruda, Opdivo); and
      2. BRAF inhibitor (e.g., Braftovi, Tafinlar, Zelboraf) with or without a MEK inhibitor (e.g., Cotellic, Mekinist, Mektovi) if BRAF V600 mutation positive; and
   2. The member has not received previous treatment with the requested medication; and
   3. The member does not have uveal or ocular melanoma; and
   4. The member does not have uncontrolled brain metastases; and
   5. The member has not had organ allograft (except kidney transplant) or prior cell transfer; and
   6. The member has adequate and stable kidney, pulmonary and cardiac function; and
   7. The member has an ECOG performance status of 0 or 1; and
   8. The member does not have clinically significant active infection.

   Aetna considers all other indications as experimental, investigational, or unproven.

2. Continuation of Therapy

   See Dosage and Administration information.

Dosage and Administration

Lifileucel is supplied as Amtagvi, a cell suspension, for intravenous infusion. A single dose of Amtagvi contains 7.5 x 10⁹ to 72 x 10⁹ viable cells suspended in 1 to 4 person-specific infusion bag(s). Amtagvi is for autologous and intravenous use only. Verify the person's identity prior to infusion. Amtagvi is provided as a single dose for infusion.

• Administer Amtagvi in an in person hospital setting with an intensive care facility.
• The Amtagvi dose is between 7.5 x 10⁹ and 72 x 10⁹ viable cells.
• Administer a lymphodepleting regimen before infusion of Amtagvi.
• Do not use a leukocyte depleting filer with Amtagvi.
• Premedicate the person with acetaminophen, or equivalent, and diphenhydramine, or another H1-antihistamine.
• Avoid prophylactic use of systemic corticosteroids.
• Administer entire dose of Amtagvi.
• Administer IL-2 (aldesleukin) after infusion of Amtagvi.
• See full prescribing information for instructions on receipt, preparation, and administration of Amtagvi.

Source: Iovance Biotherapeutics Manufacturing, 2024

Background

U.S. Food and Drug Administration (FDA)-Approved Indications

• Amtagvi is indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor.

Lifileucel is available as Amtagvi (Iovance Biotherapeutics Manufacturing LLC) and is a tumor-derived autologous T cell immunotherapy made up of a suspension of tumor-derived T cells for intravenous infusion. Amtagvi is made from resected patient tumor tissue prosected from one or more tumor lesions. Immune cells are derived from a patient's tumor(s) and then expanded in cell culture, washed, formulated a cell suspension, and cryopreserved. The product must pass a sterility test prior to release for shipping as a frozen suspension in 1 to 4 patient-specific infusion bag(s) in individual protective metal cassettes. The product is thawed before administration back into the same patient (Iovance Biotherapeutics Manufacturing, 2024).

Amtagvi is primarily made up of T cells of the CD4+T and CD8+T cell lineages. Amtagvi may also contain monocytes and other lymphocytes, including B cells and NK cells. Additionally, Amtagvi may contain melanoma tumor cells from the original tumor tissue used to manufacture the product (Iovance Biotherapeutics Manufacturing, 2024).

According to the prescribing information, Amtagvi carries the following black box warnings: treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment.

Amtagvi carries warnings and precautions for hypersensitivity reactions. Monitor for hypersensitivity reactions during infusion.

The most common (incidence of greater than or equal to 20%) adverse reactions per the prescribing information are non-laboratory adverse reactions in order of decreasing frequency were chills, pyrexia, fatigue, tachycardia, diarrhea, febrile neutropenia, edema, rash, hypotension, alopecia, infection, hypoxia, and dyspnea.

On February 16, 2024, the U.S. Food and Drug Administration granted accelerated approval to lifileucel (Amtagvi) for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 positive, a BRAF inhibitor with or without a MEK inhibitor (FDA, 2024).

Investigators evaluated the safety and efficacy of a single treatment with Amtagvi in a global, multicenter, multicohort, open-label, single-arm trial in patients with unresectable or metastatic melanoma who had previously been treated with at least one systemic therapy, including a PD-1 blocking antibody, and if BRAF V600 mutation-positive, a BRAF inhibitor with or without a MEK inhibitor. This trial excluded patients with uncontrolled brain metastases, organ allograft or prior cell transfer, melanoma of uveal or ocular origin, systemic steroid therapy for any reason, Grade 2 or higher hemorrhage within 14 days prior to study enrollment (tumor resection), left ventricular ejection fraction (LVEF) less than 45% or New York Heart Association (NYHA) functional classification greater than Class 1, and patients with forced expiratory volume in one second (FEV1) of less than or equal to 60%. Among the 89 patients who received Amtagvi, two patients were excluded because the product did not meet specification and five patients were excluded due to product comparability. Amtagvi was given following a lymphodepleting regimen consisting of cyclophosphamide 60 mg/kg daily with mesna for 2 days followed by fludarabine 25 mg/m² daily for 5 days. Three to 24 hours after infusion, patients received IL-2 (aldesleukin) at 600,000 IU/kg every 8 to 12 hours for up to 6 doses in order to support cell expansion in vivo. The median administered Amtagvi dose was 21.1 x 10⁹ viable cells. The median number of administered IL-2 (aldesleukin) doses was 6 (FDA, 2024; Iovance Biotherapeutics Manufacturing, 2024).

The main efficacy outcome measures were objective response rate (ORR) and duration of response (DoR). The primary efficacy analysis set included 82 patients who received Amtagvi. The median time to initial response to Amtagvi was 1.5 months. ORR was based on 73 patients who received Amtagvi within the recommended dosing range of 7.5 x 10⁹ to 72 x 10⁹ viable cells. ORR was 31.5% (95% confidence interval [CI]: 21.1, 43.4) and median DoR was not reached (NR) (95% CI: 4.1 months, NR) (FDA, 2024; Iovance Biotherapeutics Manufacturing, 2024).

References