Brand name: Tecelra
Drug class: Gene Therapy

Medically reviewed by Drugs.com on Dec 10, 2024. Written by ASHP.

Introduction

Afamitresgene autoleucel is a melanoma-associated antigen A4 (MAGE-A4)-directed genetically modified autologous T cell immunotherapy.

Uses for Afamitresgene Autoleucel

Afamitresgene autoleucel has the following uses:

Afamitresgene autoleucel is 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 melanoma-associated antigen A4 (MAGE-A4) as determined by FDA-approved or cleared companion diagnostic devices. Afamitresgene autoleucel has been designated an orphan drug by FDA for the treatment of soft tissue sarcoma.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Afamitresgene autoleucel is an autologous T-cell receptor (TCR) based therapy prepared from the patient’s peripheral blood mononuclear cells (PBMCs) obtained via a standard leukapheresis procedure. The PBMCs are enriched for T cells and then transduced with a replication-incompetent lentiviral vector (LV) containing the MAGE-A4 TCR transgene.

Efficacy of afamitresgene autoleucel was evaluated in a multicenter, single-arm, open-label clinical trial (SPEARHEAD-1, Cohort 1). A total of 44 patients underwent leukapheresis and received a single infusion of afamitresgene autoleucel. Overall response rate (ORR) according to RECISTv1.1 evaluated by independent review committee (IRC) was 43.2% in the treated population; 2 patients (4.5%) had a complete response and 17 patients (38.6%) had a partial response. The median duration of response was 6 months; 45.6% of patients had a duration of response of 6 months or more and 39% of patients had a duration of response of 12 months or more.

Afamitresgene Autoleucel Dosage and Administration

General

Afamitresgene autoleucel is available in the following dosage form(s) and strength(s):

• Afamitresgene autoleucel is a cell suspension for IV infusion.

• Supplied in one or more infusion bag(s) containing 2.68 x 10⁹ to 10 x 10⁹ MAGE-A4 TCR positive T cells.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

For autologous use only. For IV use only.

• Verify patient’s identity prior to infusion. Check that the patient’s identity matches the patient identifiers on the infusion bag.

• Administer a lymphodepleting regimen of cyclophosphamide and fludarabine before infusion of afamitresgene autoleucel.

• Premedicate with acetaminophen and an H1-antihistamine approximately 30-60 minutes prior to afamitresgene autoleucel infusion.

• The recommended dose of afamitresgene autoleucel is between 2.68 x 10⁹ to 10 x 10⁹ MAGE-A4 T cell receptor (TCR) positive T cells administered as a single IV infusion.

• Administer each infusion bag within one hour of thawing. The infusion may take up to 60 minutes for each infusion bag.

• DO NOT USE a leukodepleting filter.

• DO NOT USE prophylactic systemic corticosteroids.

• See Full Prescribing Information for additional details on preparation and administration.

Cautions for Afamitresgene Autoleucel

Contraindications

DO NOT use afamitresgene autoleucel in adults who are heterozygous or homozygous for HLA-A*02:05P.

Warnings/Precautions

Cytokine Release Syndrome

Cytokine release syndrome (CRS), including potentially life-threatening reaction has been observed following administration of afamitresgene autoleucel. CRS occurred in 75% of patients, 2% of whom had Grade ≥ 3 CRS. The median time to onset was 2 days (range: 1 to 5 days) and the median time to resolution was 3 days (range: 1 to 14 days). The most common symptoms were fever (97%), tachycardia (52%), hypotension (30%), nausea/vomiting (21%) and headache (15%). Tocilizumab was used to manage CRS (including Grade 1) in 55% of the patients. Thirteen patients received one dose and five patients received more than one dose. Of the five patients who received more than one dose of tocilizumab, two patients received dexamethasone in addition to tocilizumab.

Ensure that healthcare providers administering afamitresgene autoleucel have immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions.

During and following afamitresgene autoleucel administration, closely monitor patients for signs and symptoms of CRS. Following treatment with afamitresgene autoleucel, monitor patients for at least 7 days at the healthcare facility for CRS. Continue to monitor patients for CRS for at least 4 weeks following treatment with afamitresgene autoleucel. Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines.

Immune Effector Cell-associated Neurotoxicity Syndrome

Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) has been observed following administration of afamitresgene autoleucel. One patient (2%) had Grade 1 ICANS. Time to onset was two days and time to resolution was one day. Symptoms included mild mental status changes. Other symptoms may include disorientation to time and place, mild drowsiness, mild inattention. Severe symptoms may include altered level of consciousness, seizures, cerebral edema, impairment of cognitive skills, progressive aphasia, motor weakness.

Ensure that healthcare providers administering afamitresgene autoleucel have immediate access to medications and resuscitative equipment to manage ICANS.

During and following afamitresgene autoleucel administration, closely monitor patients for signs and symptoms of ICANS. Following treatment with afamitresgene autoleucel, monitor patients for at least 7 days at the healthcare facility for ICANS. Continue to monitor patients for ICANS for at least 4 weeks following treatment with afamitresgene autoleucel. Counsel patients to seek medical attention should signs or symptoms of ICANS occur. At the first sign of ICANS, immediately evaluate patients for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines.

Due to the potential for neurologic events, including dizziness and presyncope, patients receiving afamitresgene autoleucel are at risk for altered or decreased coordination in the 4 weeks following infusion.

Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Prolonged Severe Cytopenia

Patients may exhibit severe cytopenias, including neutropenia and thrombocytopenia.

Patients exhibited anemia, neutropenia, and/or thrombocytopenia for several weeks following lymphodepleting chemotherapy and afamitresgene autoleucel infusion. Patients with Grade ≥ 3 cytopenia not resolved by week 4 included anemia (9%), neutropenia (11%), and thrombocytopenia (5%). The median time to resolution was 7.3 weeks (range: 6.1 to 8.4 weeks) for anemia, 9.3 weeks (range: 6.4 to 12.3 weeks) for neutropenia and 6.3 weeks (range: 6.1 to 6.4 weeks) for thrombocytopenia.

Monitor blood counts after afamitresgene autoleucel infusion. Manage cytopenia with growth factor and blood product transfusion according to local institutional guidelines/clinical practice.

Infections

Infections may occur following lymphodepleting chemotherapy and afamitresgene autoleucel infusion. Infections (all grades) occurred in 32% of patients with synovial sarcoma. Grade 3 or higher infections occurred in 14% of patients.

Do not administer afamitresgene autoleucel to patients with active infections and/or inflammatory disorders.

Monitor patients for signs and symptoms of infection before and after afamitresgene autoleucel infusion and treat patients appropriately.

Febrile neutropenia was observed in patients after afamitresgene autoleucel infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated.

Viral reactivation has occurred in patients following treatment with afamitresgene autoleucel. Perform screening for Epstein-Barr Virus, Cytomegalovirus, Hepatitis B Virus, Hepatitis C Virus, Human Immunodeficiency Virus, and any other infectious agents if clinically indicated. Consider antiviral therapy to prevent viral reactivation per local guidelines.

Secondary Malignancies

Patients treated with afamitresgene autoleucel may develop secondary malignancies or recurrence of their cancer. Monitor for secondary malignancies.

In the event that a secondary malignancy occurs, contact Adaptimmune at 1-855-24MYADAP (1-855-246-9232) to obtain instructions on patient samples to collect for testing.

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) in afamitresgene autoleucel. Observe patients for hypersensitivity reactions during infusion.

Potential For HIV Nucleic Acid Test False-positive Results

The lentiviral vector used to make afamitresgene autoleucel has limited, short spans of genetic material which are identical to HIV. Therefore, some commercial HIV nucleic acid tests may yield false-positive results in patients who have received afamitresgene autoleucel.

Specific Populations

Pregnancy

There are no available data with afamitresgene autoleucel use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with afamitresgene autoleucel to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known if afamitresgene autoleucel has the potential to be transferred to the fetus and cause fetal toxicity. Therefore, afamitresgene autoleucel is not recommended for women who are pregnant, and pregnancy after afamitresgene autoleucel administration should be discussed with the treating physician. Report all pregnancies following treatment with afamitresgene autoleucel to Adaptimmune at 1-855-24MYADAP (1-855-246-9232).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Lactation

There is no information regarding the presence of afamitresgene autoleucel in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for afamitresgene autoleucel and any potential adverse effects on the breastfed infant from afamitresgene autoleucel or from the underlying maternal condition.

Females and Males of Reproductive Potential

Verify pregnancy status of females with reproductive potential prior to starting treatment with afamitresgene autoleucel.

There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with afamitresgene autoleucel.

Pediatric Use

The safety and effectiveness of afamitresgene autoleucel have not been established in pediatric patients.

Geriatric Use

Of the 44 patients with synovial sarcoma in the SPEARHEAD-1 study that received afamitresgene autoleucel, 6.8% were 65 years of age or older. Clinical studies of afamitresgene autoleucel did not include sufficient numbers of patients 65 years of age and over to conclude whether they respond differently from younger patients.

Common Adverse Effects

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.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

None.

Actions

Mechanism of Action

Afamitresgene autoleucel is a genetically modified autologous T cell immunotherapy consisting of CD4 and CD8 positive T cells transduced with a self-inactivating LV to express an affinity- enhanced TCR specific for human 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 afamitresgene autoleucel via TCR- peptide-HLA-A*02 complex results in T cell proliferation, cytokine secretion, and killing of MAGE-A4/HLA-A*02 expressing synovial sarcoma cells.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling.

• Inform patients that there is a chance of manufacturing or delivery failure (approximately 8% in the clinical trial). Therefore, a second manufacture of afamitresgene autoleucel may be attempted.

• Inform patients that additional therapy (other than lymphodepletion) may be necessary before afamitresgene autoleucel manufacturing is completed. This may increase the risk of adverse reactions during the pre-infusion period, which could delay or prevent administration of afamitresgene autoleucel.

• Inform patients that following infusion, it will be necessary to be monitored daily at the healthcare facility for at least 7 days for signs and symptoms of cytokine release syndrome (CRS). Patients must remain within proximity of a healthcare facility for at least 4 weeks following infusion.

• Advise patients to seek immediate medical attention if CRS occurs. Inform patients that symptoms may include fever, rigors, fast heartbeat, irregular heartbeat, low blood pressure, lightheadedness or dizziness, shortness of breath, nausea/vomiting, diarrhea, and headache.

• Advise patients to seek immediate medical attention if Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) occurs. Inform patients that symptoms may include confusion, depressed level of consciousness, delirium, seizures, or language difficulty.

• Advise patients to seek immediate medical attention if bone marrow suppression and prolonged severe cytopenias occur. Inform patients that symptoms may include bleeding or bruising, tiredness, shortness of breath, fever, pain, or redness for several weeks following lymphodepleting chemotherapy. Blood counts before and after afamitresgene autoleucel infusion should be periodically monitored.

• Advise patients to seek immediate medical attention if infections occur. Inform patients that they may exhibit signs or symptoms associated with infection, and that past infections can be reactivated following treatment with afamitresgene autoleucel.

• Advise patients to contact Adaptimmune at 1-855-24MYADAP (1-855-246-9232) if they are diagnosed with a secondary malignancy.

• Advise patients to refrain from driving or operating heavy or potentially dangerous machines for at least 4 weeks after afamitresgene autoleucel administration.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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