Afamitresgene Autoleucel

Afamitresgene Autoleucel is a prescription medication indicated for unresectable or metastatic melanoma-associated antigen A4 (MAGE-A4)-positive synovial sarcoma in adults who are HLA-A*02:01P, HLA-A*02:02P, HLA-A*02:03P, or HLA-A*02:06P positive and have received prior chemotherapy.

• Afamitresgene Autoleucel is available under the following different brand names: Tecelra.

Common side effects of Afamitresgene Autoleucel include:

• cytokine release syndrome 
• nausea
• vomiting 
• fatigue
• infections 
• pyrexia
• constipation
• dyspnea
• abdominal pain
• non-cardiac chest pain 
• decreased appetite
• tachycardia 
• back pain 
• hypotension
• diarrhea
• edema

Serious side effects of Afamitresgene Autoleucel include:

• cytokine release syndrome 
• pleural effusion
• hypersensitivity reactions
• infections
• neutropenia
• thrombocytopenia

Rare side effects of Afamitresgene Autoleucel include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injection, suspension

• 2.68-10 x 109 MAGE-A4 TCR-positive T cells in 1 or more patient-specific infusion bag(s)
• Each 250-mL infusion bag is contained in a protective metal cassette

Synovial sarcoma

Adult dosage

• 2.68-10 x 109 MAGE-A4 T-cell receptor (TCR)-positive T cells IV as a single dose
• Premedicate with acetaminophen and H1-antihistamine approximately 30-60 mins before infusion
• Administer on Day 1 following lymphodepleting therapy

Lymphodepleting chemotherapy

• Fludarabine 30 mg/m2 IV once a day for 4 days (on Days -7, -6, -5, and -4) AND
• Cyclophosphamide 600 mg/m2 IV once a day for 3 days (on Days -7, -6, and -5)
• Granulocyte-colony stimulating factors may be considered more than 24 hours after the last dose of lymphodepleting chemotherapy

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Afamitresgene Autoleucel has no noted severe interactions with any other drugs
• Afamitresgene Autoleucel has no noted serious interactions with any other drugs
• Afamitresgene Autoleucel has no noted moderate interactions with any other drugs
• Afamitresgene Autoleucel has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Heterozygous or homozygous for HLA-A*02:05P

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Afamitresgene Autoleucel?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Afamitresgene Autoleucel?”

Cautions

• Cytokine release syndrome (CRS)
• Common symptoms include fever, tachycardia, hypotension, nausea/vomiting, and headache
• Median time to onset, 2 days (range, 1-5); median time to resolution, 3 days (range, 1-14)
• Ensure patients are euvolemic before starting infusion
• Monitor for signs and symptoms of CRS during infusion, at a healthcare facility daily for at least 7 days following infusion, and then for at least 4 weeks after infusion
• Start supportive care and manage per current practice guidelines if CRS develops; hospitalization may be necessary
• Tocilizumab was used for CRS management in some patients
• Immune effector cell-associated neurotoxicity syndrome (ICANS)
• ICANS reported
  • Symptoms may include mild mental status changes, drowsiness, or inattention
  • Severe symptoms may also occur (eg, disorientation to time and place, altered consciousness, seizures, cerebral edema, cognitive impairment, progressive, aphasia, or motor weakness)
  • Ensure healthcare providers have immediate access to medications and resuscitative equipment to manage ICANS
  • Monitor for signs and symptoms of ICANS during infusion, at a healthcare facility daily for at least 7 days following infusion, and then for at least 4 weeks after infusion
  • Start supportive care and manage per current practice guidelines if ICANS develops; hospitalization may be necessary
• Driving or machine use
  • Neurologic effects (eg, dizziness, presyncope, altered or decreased coordination) may occur
  • Advise patients not to drive or engage in hazardous occupations or activities (eg, operating heavy or potentially dangerous machinery) for 4 weeks after infusion
• Prolonged severe cytopenia
  • Anemia, neutropenia, and thrombocytopenia lasting 4 weeks or longer can occur
  • Monitor blood counts after infusion
  • Manage growth factors and transfusions per local institutional guidelines or clinical practice
• Infection
  • Infections reported; febrile neutropenia may occur concurrently with CRS
  • Monitor for signs and symptoms of infection before and after infusion
  • Avoid in patients with active infections or inflammatory disorders
  • Treat infection and manage febrile neutropenia as medically indicated (eg, broad-spectrum antibiotics, fluids, and other supportive care)
  • Viral reactivation may occur; screen for Epstein-Barr virus, cytomegalovirus, hepatitis B and C viruses, human immunodeficiency virus (HIV), and other infectious agents as clinically indicated
  • Consider antiviral prophylaxis to prevent viral reactivation
• Secondary malignancies
  • Secondary malignancies or cancer recurrence may occur
  • Monitor for secondary malignancies
  • Contact Adaptimmune at 1-855-246-9232 for instructions on patient sample collection and testing if a secondary malignancy develops
• Hypersensitivity reactions
  • Product contains dimethyl sulfoxide; serious hypersensitivity reactions (eg, anaphylaxis) may occur
  • Premedicate with acetaminophen and H1-antihistamine approximately 30-60 mins before infusion
  • Monitor for hypersensitivity reactions during infusion
• HIV nucleic acid tests
  • HIV and the lentivirus used to make Afamitresgene Autoleucel have limited, short spans of identical genetic material
  • Commercial HIV nucleic acid tests may yield false-positive results

Pregnancy and Lactation

• No data available in pregnant women or from animal reproductive and developmental toxicity studies
• Perform pregnancy tests before therapy in women of reproductive potential
• Not recommended in pregnancy; unknown if Afamitresgene Autoleucel can be transferred to the fetus and cause fetal toxicity
• Report pregnancy following infusion to Adaptimmune at 1-855-246-9232
• Lactation
  • No data is available on the presence of human milk, its effects on breastfed infants, or its effects on milk production
  • Consider developmental and health benefits of breastfeeding and potential adverse effects on breastfed infants from therapy or underlying maternal condition along with the patient’s clinical need for therapy