Afamitresgene Autoleucel (Tecelra)

Number: 1068

Table Of Contents

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

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses afamitresgene autoleucel (Tecelra) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of afamitresgene autoleucel (Tecelra) is required of all Aetna participating providers and members in applicable plan designs. For precertification of afamitresgene autoleucel (Tecelra), 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 afamitresgene autoleucel (Tecelra), see Aetna Institutes® GCIT Designated Centers. 

1. Criteria for Initial Approval

   Synovial Sarcoma

   Aetna considers afamitresgene autoleucel (Tecelra) medically necessary for treatment of unresectable or metastatic synovial sarcoma in members 18 years and older when all of the following criteria are met:

   1. The member has received prior treatment with chemotherapy; and
   2. The tumor is HLA-A*02:01P, HLA-A*02:02P, HLA-A*02:03P, or HLA-A*02:06P allele positive; and
   3. The tumor expresses the MAGE-A4 antigen; and
   4. The member has not received previous treatment with the requested medication; and
   5. The member is not heterozygous or homozygous for HLA-A*02:05P; and 
   6. The member has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; and
   7. The member has adequate and stable cardiac and kidney function; and
   8. The member has not had an allogeneic hematopoietic stem cell transplant; and
   9. The member does not have a clinically significant active infection and/or inflammatory disorder.

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

2. Continuation of Therapy

   See Dosage and Administration information.

Dosage and Administration

Afamitresgene autoleucel is supplied as Tecelra cell suspension for autologous intravenous infusion only. Tecelra is provided in one or more infusion bag(s) containing 2.68 x 10⁹ to 10 x 10⁹ melanoma-associated antigen A4 (MAGE-A4) T cell receptor (TCR) positive T cells.

The recommended dose is between 2.68 x 10⁹ to 10 x 10⁹ MAGE-A4 TCR positive T cells administered as a single intravenous infusion. Tecelra is provided as a single dose for infusion in one or more infusion bag(s). Verify the number of bags received for the indicated dose prior to preparation for infusion.

Refer to the full prescribing information for Tecelra for preparation and administration instructions.

Source: Adaptimmune, 2024

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
80069	Renal function panel
96413	Chemotherapy administration, IV infusion technique; up to 1 hour, single or initial substance/drug
96415	each additional hour (list in addition to code for primary procedure)
HCPCS codes covered if selection criteria are met:
Afamitresgene autoleucel (Tecelra) – no specific code
Other HCPCS codes related to the CPB:
S2142	Cord blood-derived stem-cell transplantation, allogeneic
S2150	Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including: pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and the number of days of pre-and post-transplant care in the global definition
ICD-10 codes covered if selection criteria are met:
C49.0 - C49.9	Malignant neoplasm of other connective and soft tissue [Synovial sarcoma]

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Background

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

• Tecelra is a melanoma-associated antigen A4 (MAGE-A4)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are human leukocyte antigen (HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P) positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices.

Afamitresgene autoleucel is available as Tecelra (Adaptimmune, LLC), a genetically modified autologous T cell immunotherapy consisting of CD4 and CD8 positive T cells transduced with a self-inactivating lentiviral vector (LV) to express an affinity-enhanced T cell receptor (TCR) specific for human melanoma-associated antigen A4 (MAGE-A4) on the cell surface. The TCR recognizes an HLA-A*02 restricted MAGE-A4 peptide. MAGE-A4 is an intracellular cancer-testis antigen that has restricted expression in normal tissues and is expressed in synovial sarcoma. Antigen-specific activation of Tecelra via TCR- peptide-HLA-A*02 complex results in T cell proliferation, cytokine secretion, and killing of MAGEA4/HLA-A*02 expressing synovial sarcoma cells (Adaptimmune, 2024).

According to the prescribing information, Tecelra carries the boxed warning for cytokine release syndrome (CRS), which may be severe or life-threatening in patients receiving this drug. At first sign of CRS, immediately evaluate the patient for hospitalization and initiate treatment with supportive care. Ensure that healthcare providers administering Tecelra have immediate access to medications and resuscitative equipment to manage CRS.

In addition, Tecelra use is contraindicated in adults who are heterozygous or homozygous for HLA-A*02:05P.

The prescribing information notes the following warnings and precautions:

• Immune effector cell-associated neurotoxicity syndrome (ICANS): Monitor for ICANS events for at least 4 weeks after treatment with Tecelra.
• Prolonged severe cytopenia: Patients may exhibit cytopenia (hemoglobin < 8.0 g/dL, neutrophils < 1,000/mm3, platelets < 50,000/mm3) for several weeks following lymphodepleting chemotherapy and Tecelra infusion. Monitor blood counts prior to and after Tecelra infusion.
• Infections: Monitor patients for signs and symptoms of infection; treat appropriately.
• Secondary malignancies: In the event that a secondary malignancy occurs after treatment with Tecelra, contact the manufacturer designated contact number.
• Hypersensitivity reactions: Monitor for hypersensitivity reactions during infusion.
• Effects on ability to drive and use machines: Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, for at least 4 weeks after receiving Tecelra.

Furthermore, the most common adverse reactions (≥ 20%) were, cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, and edema. Grade 3 or 4 laboratory abnormalities (≥ 20%) were lymphocyte count decreased, neutrophil count decreased, white cell blood count decreased, red blood cell decreased, and platelet count decreased. The most common serious adverse reactions (≥ 5%) were cytokine release syndrome and pleural effusion.

According to the National Cancer Institute (NCI) website (https://www.cancer.gov), synovial sarcoma, also known as malignant synovioma, is characterized as a cancer originating from different types of soft tissue, such as muscle or ligaments. It can occur in the arm, leg, or foot, and near joints such as the wrist or ankle. Additionally, it can appear in soft tissues in the lung or abdomen. An estimated 5% to 10% of soft-tissue tumors are synovial sarcoma. In the U.S., one to two persons out of every one million are diagnosed with synovial sarcoma. One third of synovial sarcoma diagnoses occur under the age of 30. It is somewhat more frequent in males. Imaging modalities that are used to take pictures of the tumor for patients presenting with symptoms of synovial sarcoma include x-ray, ultrasound, computed tomography scan, magnetic resonance imaging. Tumor biopsy can aid the pathologist in determining what kind of tumor is present. Synovial sarcoma treatment is dependent on whether the disease has spread. Treatment options include surgery (first choice of treatment), radiation therapy, and chemotherapy. The NCI approximates that anywhere from 36% to 76% of individuals with synovial sarcoma will be alive five years after their first diagnosis. Survival chances increase if the tumor is completely removed and does not return or spread.

On August 2, 2024, the U.S. Food and Drug Administration granted accelerated approval to afamitresgene autoleucel (Tecelra) for the treatment of adults with with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the melanoma-associated antigen A4 (MAGE-A4) as determined by FDA-approved or cleared companion diagnostic devices. The FDA approval was based on supporting data from the SPEARHEAD-1, Cohort 1 study (FDA, 2024b).

In the SPEARHEAD-1, Cohort 1 study, a multicenter, single-arm, open-label, non-randomized, phase 2 clinical trial, D'Angelo et al. (2024), evaluated the efficacy of afamitresgene autoleucel (Tecelra) for the treatment of patients with HLA-A*02 and MAGE-A4-expressing advanced synovial sarcoma or myxoid round cell liposarcoma. The study enrolled HLA-A*02:01P, HLA-A*02:02P, HLA-A*02:03P, and HLA-A*02:06P allele positive patients with inoperable or metastatic synovial sarcoma who had received prior systemic therapy with either doxorubicin and/or ifosfamide and whose tumor expressed the MAGE-A4 tumor antigen. The study consisted of three cohorts, of which the primary investigational cohort (cohort 1) included 52 patients with HLA-A*02, aged 16-75 years, with cytogenetically confirmed metastatic or unresectable synovial sarcoma (n = 44) or myxoid round cell liposarcoma (n = 8) expressing MAGE-A4, and who had received at least one previous line of anthracycline-containing or ifosfamide-containing chemotherapy. The median number of prior lines of systemic therapies was three (interquartile range: two to four). A total of 44 patients with synovial sarcoma in cohort 1 received a single infusion of Tecelra (transduced dose range 1.0 x 10⁹ to 10.0 x 10⁹ T cells) after lymphodepleting chemotherapy with fludarabine and cyclophosphamide. The major efficacy endpoint measure was overall response rate (ORR) evaluated by independent review committee using Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1) and duration of response (DOR) was a secondary efficacy endpoint measure for cohort 1. In cohort 1, the ORR was 43.2% (95% Confidence Interval [CI]: 28.4, 59.0). The median time to response was 4.9 weeks (95% CI: 4.4 weeks, 8 weeks). The median DOR was 6 months (95% CI: 4.6, not reached). Out of the patients who responded to treatment, 45.6% and 39.0% had a duration of response greater than or equal to 6 months and 12 months, respectively. The investigators concluded that Tecelra treatment demonstrated durable responses in heavily pretreated patients with with HLA-A*02 and MAGE-A4-expressing synovial sarcoma (Adaptimmune, 2024; FDA, 2024b).

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References