Version July 2025
Cytokine release syndrome (CRS), which may be severe or life-threatening, occurred in patients receiving afamitresgene autoleucel. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care. Ensure that healthcare providers administering afamitresgene autoleucel have immediate access to medications and resuscitative equipment to manage CRS.
Dosage guidance:
Safety: For autologous use only. Confirm patient identity matches cassette(s) and infusion bag(s) prior to infusion. Confirm availability of afamitresgene autoleucel prior to initiating lymphodepleting chemotherapy. Confirm that medications and emergency equipment for management of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are available prior to afamitresgene autoleucel infusion and during recovery period. Ensure patients are euvolemic prior to initiating afamitresgene autoleucel infusion. Premedicate with acetaminophen and an H1 antihistamine 30 to 60 minutes prior to afamitresgene autoleucel infusion. Avoid prophylactic systemic corticosteroids, as corticosteroids may interfere with afamitresgene autoleucel activity.
Dosage form information: Afamitresgene autoleucel is provided as a single dose for infusion in one or more infusion bags. Prior to preparation, verify the number of bags received for the indicated dose.
Clinical considerations: A treatment course consists of 1) lymphodepleting chemotherapy (with fludarabine for 4 days and cyclophosphamide for 3 days), and 2) afamitresgene autoleucel infusion 4 days after completion of lymphodepleting chemotherapy. Short-acting or pegylated granulocyte stimulating factor (G-CSF) may be administered 24 hours after the last day of lymphodepleting chemotherapy and continued until resolution of neutropenia per institutional standards at the discretion of the provider. Consider antiviral therapy to prevent viral reactivation as appropriate per local guidelines.
Synovial sarcoma, unresectable or metastatic, relapsed or refractory, HLA-A*02:01P, HLA-A*02:02P, HLA-A*02:03P, or HLA-A*02:06P positive, MAGE-A4 positive:
Note: Do not administer afamitresgene autoleucel in patients with active infections and/or inflammatory conditions.
IV: Target dose: 2.68 × 109 to 10 × 109 MAGE-A4 T cell receptor–positive T cells.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Cytokine release syndrome: At first signs of cytokine release syndrome (CRS), immediately evaluate patient for hospitalization, institute supportive care management based on severity, and consider further management per current practice guidelines (Ref).
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Cytokine release syndrome grade |
Management |
|---|---|
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a D’Angelo 2024. | |
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Grade 1: Constitutional symptoms not life-threatening (eg, fever, nausea, fatigue, headache, myalgias, malaise) |
Supportive care management including fluid balance monitoring and maintenance of adequate hydration and blood pressure. Assess and treat possible infection per institutional practice. Administer antipyretics and/or analgesics as needed. Consider anti-IL6 therapy (tocilizumab 8 mg/kg [maximum dose: 800 mg] IV) if clinically indicated (symptoms persisting ≥24 hours, older age, or comorbidities). Corticosteroids or other immunosuppressant therapies (eg, TNF alpha and IL-1 receptor inhibitors) may be used in anti-IL-6-refractory patients. |
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Grade 2: Symptoms require and respond to moderate intervention. Hypoxia with oxygen requirement <40% FiO2, or hypotension responsive to fluids or low dose of one vasopressor, or grade 2 organ toxicity |
Supportive care management including fluid balance monitoring and maintenance of adequate hydration and blood pressure. Assess and treat possible infection per institutional practice. Administer antipyretics and/or analgesics as needed. Monitor cardiac and other organ function. Manage hypotension with fluid and vasopressors. Administer oxygen for hypoxia. Administer anti-IL6 therapy (tocilizumab 8 mg/kg [maximum dose: 800 mg] IV or siltuximab 11 mg/kg IV) if clinically indicated (symptoms persisting ≥24 hours, older age, or comorbidities). Corticosteroids or other immunosuppressant therapies (eg, TNF alpha and IL-1 receptor inhibitors) may be used in anti-IL-6-refractory patients. |
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Grade 3: Symptoms require and respond to aggressive intervention. Oxygen requirement ≥40% FiO2, or hypotension requiring high-dose or multiple vasopressors, or grade 3 organ toxicity, or grade 4 transaminitis |
Consider intensive care monitoring or monitor very closely for cardiac and other organ dysfunction. Supportive care management including fluid balance monitoring and maintenance of adequate hydration and blood pressure. Assess and treat possible infection per institutional practice. Administer antipyretics and/or analgesics as needed. Manage hypotension with fluid and vasopressors. Administer oxygen for hypoxia. Administer anti-IL6 therapy (tocilizumab 8 mg/kg [maximum dose: 800 mg] IV or siltuximab 11 mg/kg IV). Corticosteroids or other immunosuppressant therapies (eg, TNF alpha and IL-1 receptor inhibitors) may be used in anti-IL-6-refractory patients. |
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Grade 4: Life-threatening symptoms or grade 4 organ toxicity (excluding transaminitis) |
Intensive care management indicated including mechanical ventilation, fluids, vasopressors, antibiotics, and other measures as indicated. Administer anti-IL6 therapy (tocilizumab 8 mg/kg [maximum dose: 800 mg] IV or siltuximab 11 mg/kg IV). Corticosteroids or other immunosuppressant therapies (eg, TNF alpha and IL-1 receptor inhibitors) may be used in anti-IL-6-refractory patients. |
Neurotoxicity (immune effector cell–associated neurotoxicity syndrome [ICANS]): At first signs of ICANS, immediately evaluate patient for hospitalization, institute supportive care management based on severity, and consider further management per current practice guidelines (Ref).
|
ICANS grade |
Management recommendations |
Medication specific recommendations |
|---|---|---|
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a D’Angelo 2024. | ||
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b ICANS = immune effector cell–associated neurotoxicity syndrome; CRS = cytokine release syndrome; ICP = intracranial pressure; CSF = cerebrospinal fluid. | ||
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c If patient is arousable and able to perform ICE assessment, assess: • Orientation (oriented to year, month, city, hospital = 4 points) • Naming (name 3 objects, [eg, point to clock, pen, button = 3 points]) • Follows commands (eg, "show me 2 fingers" or "close your eyes and stick out your tongue" = 1 point) • Writing (ability to write a standard sentence = 1 point) • Attention (count backwards from 100 by tens = 1 point) If patient is unarousable and unable to perform ICE assessment (Grade 4 ICANS) = 0 points. | ||
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d Intracranial hemorrhage ± associated edema is not considered a neurotoxicity feature and is excluded from ICANS grading. | ||
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e Tremors and myoclonus associated with immune effector cell therapies may be graded; however, they do not influence ICANS grading. | ||
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Grade 1 ICE score 7 to 9c or Depressed level of consciousness categorized as "awakens spontaneously" |
All patients: Supportive care management (aspiration precautions, IV hydration). Withhold oral intake of food, medications, and fluids; assess swallowing. Evaluate for contributing causes and treat accordingly. |
Avoid medications that cause CNS depression. |
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Unless symptoms are mild and transient (eg, 1 point change in ICE score for <12 hours): Neurology consultation with appropriate testing (fundoscopic exam, MRI brain, lumbar puncture [as clinically indicated], MRI spine [as clinically indicated], consider EEG [if seizure activity suspected]). |
Institute nonsedating antiseizure medications (eg, levetiracetam) for seizure prophylaxis. Consider anti-IL6 therapy (tocilizumab 8 mg/kg [maximum dose: 800 mg] IV or siltuximab 11 mg/kg IV) if clinically indicated (grade 1 symptoms persisting >24 hours or worsening with concurrent CRS). | |
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Grade 2 ICE score 3 to 6c or Depressed level of consciousness categorized as "awakens to voice" |
Supportive care management and neurologic workup as per grade 1. Consider patient transfer to ICU if ICANS associated with ≥ grade 2 CRS. |
Administer anti-IL6 therapy (tocilizumab 8 mg/kg [maximum dose: 800 mg] IV or siltuximab 11 mg/kg IV) if associated with concurrent CRS. If refractory to anti-IL6 therapy or no evidence of CRS: Consider dexamethasone 10 mg IV every 6 hours or methylprednisolone 1 mg/kg IV every 12 hours. Continue corticosteroids until improvement to grade 1, then taper. |
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Grade 3 ICE score 0 to 2c (if ICE score is 0, but the patient is arousable [eg, awake with global aphasia] and able to perform assessment) or Depressed level of consciousness categorized as "awakens only to tactile stimulus" or Seizures (any clinical seizure, focal or generalized, that resolves rapidly, or nonconvulsive seizures on EEG that resolve with intervention) or Elevated ICP: Focal/local edema on neuroimagingd |
Supportive care management and neurologic workup as per grade 1. ICU transfer recommended. Consider repeat neurologic testing every 2 to 3 days for persistent ≥ grade 3 ICANS. |
Administer anti-IL6 therapy (tocilizumab 8 mg/kg [maximum dose: 800 mg] IV or siltuximab 11 mg/kg IV) if associated with concurrent CRS and not administered previously. Worsening ICANS despite anti-IL6 therapy or ICANS without concurrent CRS: Administer corticosteroids as per grade 2. Stage 1 or 2 papilledema with CSF opening pressure <20 mm Hg: Administer corticosteroids as per grade 4. |
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Grade 4 ICE score 0c or Depressed level of consciousness categorized as "either patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or stupor or coma" or Seizures (life-threatening prolonged seizure [>5 minutes], or repetitive clinical or electrical seizures without return to baseline in between) or Motor findingse (deep focal motor weakness, such as hemiparesis or paraparesis) or Elevated ICP/cerebral edema, with signs/symptoms, such as: diffuse cerebral edema on neuroimaging, decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, or Cushing's triad |
Supportive care management and neurologic workup as per grade 1. Repeat neurologic imaging every 2 to 3 days. Consider neurosurgical consultation in patients with increased ICP. Intensive care management indicated; consider mechanical ventilation for airway protection. |
Administer anti-IL6 therapy (tocilizumab 8 mg/kg [maximum dose: 800 mg] IV or siltuximab 11 mg/kg IV) if associated with concurrent CRS and not administered previously. High dose corticosteroids (eg, methylprednisolone 1g/day IV for 3 days, followed by rapid taper [250 mg IV every 12 hours for 2 days, 125 mg IV every 12 hours for 2 days, then 60 mg IV every 12 hours for 2 days]) until improvement to grade 1. |
Other toxicities:
Cytopenias: Manage cytopenia with growth factor and blood product infusion (according to local institutional guidelines/clinical practice).
Infection: If infection occurs, manage appropriately.
Neutropenic fever: Evaluate for infection, and manage with broad-spectrum antibiotics, fluids, and other supportive care, as medically indicated.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Chest pain, edema, hypertension, hypotension, sinus tachycardia, tachycardia
Dermatologic: Alopecia
Endocrine & metabolic: Weight loss
Gastrointestinal: Abdominal pain, constipation, decreased appetite, diarrhea, nausea, vomiting
Hematologic & oncologic: Decreased neutrophils, decreased platelet count, decreased red blood cells, leukopenia, lymphocytopenia
Hepatic: Increased serum alanine aminotransferase
Hypersensitivity: Cytokine release syndrome
Infection: Infection (including viral reactivation)
Nervous system: Asthenia, chills, dizziness, fatigue, headache, noncardiac chest pain
Neuromuscular & skeletal: Back pain, limb pain
Respiratory: Cough, dyspnea
Miscellaneous: Fever
1% to 10%:
Nervous system: Neurotoxicity (immune effector cell-associated neurotoxicity syndrome [ICANS])
Respiratory: Pleural effusion
Frequency not defined: Hematologic & oncologic: Febrile neutropenia
Heterozygous or homozygous for HLA-A*02:05P.
Concerns related to adverse effects:
• Cytokine release syndrome: Cytokine release syndrome (CRS), including potentially life-threatening reactions, has occurred with afamitresgene autoleucel; grade 3 or higher CRS has also occurred in a small number of patients. The median time to onset of CRS was 2 days (range: 1 to 5 days) and the median time to resolution was 3 days (range: 1 to 14 days). In patients who experienced CRS, the most common manifestations included fever, hypotension, tachycardia, nausea/vomiting, and headache. In afamitresgene autoleucel–treated patients, CRS (including grade 1) management included tocilizumab ± dexamethasone. Patients should seek immediate medical attention if signs/symptoms of CRS occur at any time.
• Cytopenias: Severe and prolonged cytopenias, including ≥ grade 3 anemia, neutropenia, and thrombocytopenia, may occur following lymphodepleting chemotherapy and afamitresgene autoleucel. The median time to recovery after afamitresgene autoleucel infusion 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.
• Hypersensitivity: Serious hypersensitivity, including anaphylaxis, may occur with afamitresgene autoleucel; may occur secondary to dimethyl sulfoxide (DMSO) in afamitresgene autoleucel.
• Infections: Infections have occurred following afamitresgene autoleucel, including ≥ grade 3 infections. Neutropenic fever has been observed and may be concurrent with CRS. Viral reactivation has occurred in afamitresgene autoleucel–treated patients.
• Neurologic toxicities: Neurologic toxicities, including immune effector cell–associated neurotoxicity syndrome (ICANS), occurred in one patient treated with afamitresgene autoleucel. The median time to onset of neurotoxicity was 2 days and time to resolution was 1 day. Symptoms of ICANS may include mild mental status changes, disorientation to time and place, mild drowsiness, and/or mild inattention. Severe symptoms may include altered level of consciousness, seizures, cerebral edema, impairment of cognitive skills, progressive aphasia, and motor weakness. Patients should seek immediate medical attention for signs/symptoms of ICANS. 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 administration. Patients should refrain from driving and other hazardous occupations or activities for at least 4 weeks following afamitresgene autoleucel cell infusion.
• Secondary malignancies: Patients treated with afamitresgene autoleucel may develop secondary malignancies or recurrence of their cancer. If a secondary malignancy develops, contact the manufacturer (1-855-246-9232) for reporting and to obtain instructions on collection of patient samples for testing.
Dosage form specific issues:
• Dimethyl sulfoxide: Afamitresgene autoleucel contains DMSO, which is associated with serious hypersensitivity reactions, including anaphylaxis.
• Universal precautions: Afamitresgene autoleucel contains human blood cells that are genetically modified with self-inactivating lentiviral vector; follow universal precautions and facility biosafety guidelines for handling and disposal to avoid potential transmission of infectious diseases.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Tecelra: Ten billion cells (1 ea)
No
Suspension (Tecelra Intravenous)
10000000000CELLS (per each): $0.00
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Afamitresgene autoleucel must be administered at qualified treatment centers; information is available from the manufacturer at https://www.tecelra.com/hcp/authorized-treatment-center.
IV: For IV use only. Administer in a health care facility. Coordinate the timing of administration with thawing. Prime tubing set with NS prior to infusion. Infuse afamitresgene autoleucel within 1 hour after thawing. After the entire contents of infusion bag(s) have infused, rinse tubing and infusion bag with ~50 mL of NS to ensure all product is delivered. Do not use a leukodepleting filter. If more than one infusion bag is required, administer all bags as instructed, and prime and rinse with all bags. Thaw one bag at a time and do not initiate thawing of the next bag until infusion of the previous bag is complete. Apply universal precautions and facility biosafety guidelines for product handling.
Prior to administration: Confirm that medications and emergency equipment for management of cytokine release syndrome (CRS) are available prior to afamitresgene autoleucel infusion and during recovery period. Premedicate with acetaminophen and an H1 antihistamine 30 to 60 minutes prior to afamitresgene autoleucel infusion. Avoid prophylactic systemic corticosteroids, as corticosteroids may interfere with afamitresgene autoleucel activity.
Monitor patient closely (for signs/symptoms of cytokine release syndrome and neurotoxicity) at the health care facility during and following infusion and for at least 7 days after cell infusion; patient should remain within proximity of the facility for at least 4 weeks after infusion for monitoring.
Synovial sarcoma, unresectable or metastatic, relapsed or refractory, HLA-A*02:01P, HLA-A*02:02P, HLA-A*02:03P, or HLA-A*02:06P positive, and MAGE-A4 positive : Treatment of unresectable or metastatic synovial sarcoma in adults who have received prior chemotherapy, are HLA-A*02:01P, HLA-A*02:02P, HLA-A*02:03P, or HLA-A*02:06P positive (in blood samples) and whose tumor expresses the melanoma-associated antigen A4 (MAGE-A4) antigen as determined by an approved or cleared companion diagnostic device.
Afamitresgene autoleucel may be confused with axicabtagene ciloleucel, betibeglogene autotemcel, brexucabtagene autoleucel, ciltacabtagene autoleucel, elivaldogene autotemcel, exagamglogene autotemcel, idecabtagene vicleucel, lifileucel, lisocabtagene maraleucel, lovotibeglogene autotemcel, sipuleucel-T, tisagenlecleucel.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG (Intravesical): Myelosuppressive Agents may decrease therapeutic effects of BCG (Intravesical). Myelosuppressive Agents may increase adverse/toxic effects of BCG (Intravesical). Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Cladribine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to initiating treatment in patients who could become pregnant. Data are insufficient to provide recommendations for duration of contraception following administration of afamitresgene autoleucel.
Animal reproduction studies have not been conducted.
Until data become available, use is not recommended in patients who are pregnant or who plan to become pregnant. Report all pregnancies that occur following treatment to Adaptimmune (1-855-246-9232).
It is not known if afamitresgene autoleucel is present in breast milk.
According to the manufacturer, the decision to breastfeed should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Screen for Epstein-Barr virus, cytomegalovirus, hepatitis B virus (HBV), hepatitis C virus, HIV, and any other infectious agents if clinically indicated (prior to therapy). Verify pregnancy status prior to initiating treatment in patients who could become pregnant. Monitor blood counts after afamitresgene autoleucel infusion.
Monitor closely for cytokine release syndrome (CRS) and signs/symptoms of ICANS during therapy and for at least 4 weeks after infusion. Monitor patient daily (for signs/symptoms of CRS and neurotoxicity [including immune effector cell–associated neurotoxicity syndrome (ICANS) symptoms]) at the health care facility for at least 7 days after cell infusion. Monitor for signs/symptoms of infection (before and after treatment). Monitor for secondary malignancies. Monitor for hypersensitivity reactions during infusion.
The American Society of Clinical Oncology HBV screening and management provisional clinical opinion (Ref) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Afamitresgene autoleucel is a genetically modified autologous T cell immunotherapy (consisting of CD4- and CD8-positive T cells transduced with a self-inactivating lentiviral vector) expressing a T cell receptor (TCR) with enhanced affinity for melanoma-associated antigen A4 (MAGE-A4). MAGE-A4 is an intracellular cancer-testis antigen that has restricted expression in normal tissues and is expressed in synovial sarcoma. The TCR recognizes an HLA-A*02 restricted MAGE-A4 peptide. The resulting activated complex results in T cell proliferation, cytokine secretion, and killing of MAGE-A4/HLA-A*02 expressing synovial sarcoma cells.
Note: Afamitresgene autoleucel exhibits an initial engraftment and expansion phase, followed by contraction and persistence of cells with high inter-individual variability.
Onset: Median time to response: 4.9 weeks; peak serum concentrations of cytokines and soluble factors involved in T cell activation and inflammation were observed between days 3 to 8 following afamitresgene autoleucel infusion.
Time to peak: 7 days (range: 1 to 89 days).
