Version May 2024
The FDA has received reports of T-cell malignancies in patients treated with BCMA-directed or CD19-directed autologous CAR T cell immunotherapies. Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, the FDA is investigating the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action.
Further information may be found at https://www.fda.gov/safety/medical-product-safety-information/bcma-directed-or-cd19-directed-autologous-chimeric-antigen-receptor-car-t-cell-immunotherapies-fda.
Cytokine release syndrome (CRS), including life-threatening reactions, occurred in patients receiving brexucabtagene autoleucel. Do not administer brexucabtagene autoleucel to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including life-threatening reactions, occurred in patients receiving brexucabtagene autoleucel, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with brexucabtagene autoleucel. Provide supportive care and/or corticosteroids as needed.
Brexucabtagene autoleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the YESCARTA and TECARTUS REMS Program.
Dosage guidance:
Safety: For autologous use only; confirm patient identity matches cassette and infusion bag prior to infusion. Confirm availability of autologous brexucabtagene autoleucel prior to initiating lymphodepleting chemotherapy. Ensure tocilizumab (at least 2 doses) and emergency equipment are available prior to brexucabtagene autoleucel infusion and during recovery period. Premedicate with acetaminophen and diphenhydramine (or another H1-antagonist) ~30 to 60 minutes prior to brexucabtagene autoleucel infusion. Avoid prophylactic systemic corticosteroids because they may interfere with the brexucabtagene autoleucel activity.
Clinical considerations: Begin infection prophylaxis (according to local recommendations) prior to initiating brexucabtagene autoleucel. Do not administer to patients with clinically significant active systemic infection or inflammatory disorders.
Acute lymphoblastic leukemia, B-cell precursor, relapsed/refractory: Note: A treatment course consists of lymphodepleting chemotherapy (with fludarabine and cyclophosphamide) on the fourth, third, and second day prior to brexucabtagene autoleucel infusion.
IV: Target dose: 1 × 106 chimeric antigen receptor (CAR)–positive viable T cells per kg body weight (Ref); maximum dose: 1 × 108 CAR-positive viable T cells.
Mantle cell lymphoma, relapsed or refractory: Note: A treatment course consists of lymphodepleting chemotherapy (with fludarabine and cyclophosphamide) on the fifth, fourth, and third day prior to brexucabtagene autoleucel infusion.
IV: Target dose: 2 × 106 CAR-positive viable T cells per kg body weight (Ref); maximum dose: 2 × 108 CAR-positive viable 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: Note: Evaluate patients immediately at the first sign of cytokine release syndrome (CRS); if fever, hypoxia, and/or hypotension occur, evaluate for other causes, and manage as appropriate. Monitor patients with ≥ grade 2 CRS with continuous cardiac telemetry and pulse oximetry. Consider obtaining an echocardiogram in patients with severe CRS; severe or life-threatening CRS may require intensive care supportive therapy.
|
CRS Grade |
Tocilizumab |
Corticosteroids |
|---|---|---|
|
Grade 1: Symptoms require symptomatic treatment only (eg, fever, nausea, fatigue, headache, myalgia, malaise). |
If not improving after 24 hours, administer tocilizumab 8 mg/kg IV over 1 hour (maximum 800 mg/dose). |
Not indicated. |
|
Grade 2: Symptoms require and respond to moderate intervention. Oxygen requirement <40% FiO2 or hypotension responsive to fluids or low-dose of one vasopressor or grade 2 organ toxicity. |
Administer tocilizumab 8 mg/kg IV over 1 hour (maximum 800 mg/dose); may repeat every 8 hours as needed if not responsive to IV fluids or requiring increased supplemental oxygen. Maximum tocilizumab: 3 doses in 24 hours, maximum total of 4 doses if no clinical improvement in CRS signs/symptoms. If improving, discontinue tocilizumab. |
If no improvement within 24 hours after initiating tocilizumab, manage as grade 3. If improving, taper corticosteroids. |
|
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. |
Administer tocilizumab as per grade 2. If improving, discontinue tocilizumab. |
Administer methylprednisolone 1 mg/kg IV twice daily or equivalent dexamethasone (eg, 10 mg IV every 6 hours) until grade 1, then taper corticosteroids. If improving, manage as grade 2. If not improving, manage as grade 4. |
|
Grade 4: Life-threatening symptoms. Requirements for ventilator support, CVVHD or grade 4 organ toxicity (excluding transaminitis). |
Administer tocilizumab as per grade 2. If improving, discontinue tocilizumab. |
Administer methylprednisolone 1 g IV daily for 3 days; if improving, taper corticosteroids, and manage as grade 3. If not improving, consider alternate immunosuppressants. |
Neurologic toxicity: Note: Manage promptly if neurologic toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS) occur. Rule out other causes of neurologic symptoms. Monitor patients with ≥ grade 2 neurologic toxicity/ICANS with continuous cardiac telemetry and pulse oximetry. Severe or life-threatening neurologic toxicity may require intensive care supportive therapy. Consider nonsedating antiseizure medication (eg, levetiracetam) for seizure prophylaxis for any ≥ grade 2 neurologic toxicity.
|
Neurologic Event |
Concurrent CRS |
No Concurrent CRS |
|---|---|---|
|
aADLs = activities of daily living. | ||
|
Grade 1: Somnolence – mild drowsiness or sleepiness. Confusion – mild disorientation. Encephalopathy – mild limiting of ADLsa. Dysphasia – not impairing ability to communicate. |
Administer tocilizumab per previous (CRS) table for management of grade 1 CRS. |
Supportive care. |
|
Grade 2: Somnolence – moderate limiting of instrumental ADLs. Confusion – moderate disorientation. Encephalopathy – limiting instrumental ADLs. Dysphasia – moderate, impairing ability to communicate spontaneously. Seizure(s). |
Administer tocilizumab per previous (CRS) table for management of grade 2 CRS. If not improving within 24 hours of initiating tocilizumab, administer dexamethasone 10 mg IV every 6 hours until ≤ grade 1, then taper corticosteroids. If improving, discontinue tocilizumab. If still not improving, manage as grade 3. |
Administer dexamethasone 10 mg IV every 6 hours until ≤ grade 1. If improving, taper corticosteroids. |
|
Consider nonsedating antiseizure medication (eg, levetiracetam) for seizure prophylaxis. | ||
|
Grade 3: Somnolence – obtundation or stupor. Confusion – severe disorientation. Encephalopathy – limiting self-care ADLs. Dysphasia – severe receptive or expressive characteristics, impairing ability to read, write, or communicate intelligibly. |
Administer tocilizumab per previous (CRS) table for management of grade 2 CRS. In addition, administer dexamethasone 10 mg IV every 6 hours (administer the first dose with the first dose of tocilizumab); continue until ≤ grade 1, then taper corticosteroids. If improving, discontinue tocilizumab and manage as grade 2. If still not improving, manage as grade 4. |
Administer dexamethasone 10 mg IV every 6 hours; continue until ≤ grade 1, then taper corticosteroids. If not improving, manage as grade 4. |
|
Consider nonsedating antiseizure medication (eg, levetiracetam) for seizure prophylaxis. | ||
|
Grade 4: Life-threatening consequences. Urgent intervention indicated. Requirement for mechanical ventilation. Consider cerebral edema. |
Administer tocilizumab per previous (CRS) table for management of grade 2 CRS. Administer methylprednisolone 1 g IV daily for 3 days (administer the first dose with the first dose of tocilizumab). If improving, then manage as grade 3. If not improving, consider alternate immunosuppressants. |
Administer methylprednisolone 1 g IV daily for 3 days. If improving, then manage as grade 3. If not improving, consider alternate immunosuppressants. |
|
Consider nonsedating antiseizure medication (eg, levetiracetam) for seizure prophylaxis. | ||
Other adverse reactions:
Hemophagocytic lymphohistiocytosis/macrophage activation syndrome: Manage per clinical and institutional standards/guidelines.
Hypogammaglobulinemia: Manage with IV immune globulin replacement, infection precautions, and antibiotic and/or antiviral prophylaxis as indicated.
Neutropenic fever: Evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as clinically 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 with acute lymphoblastic leukemia (ALL) and/or mantle cell lymphoma (MCL).
>10%:
Cardiovascular: Cardiac arrhythmia (10% to 15%), edema (29% to 35%), hypertension (13% to 18%), hypotension (ALL: 69%; MCL: 57%), tachycardia (ALL: 63%; MCL: 45%), thrombosis (ALL: 4%; MCL: 17%)
Dermatologic: Skin rash (ALL: 31%; MCL: 9% to 22%)
Endocrine & metabolic: Hyperglycemia (grades 3/4: ALL: 22%), hypocalcemia (grades 3/4: 21% to 22%), hypokalemia (grades 3/4: 10% to 13%), hyponatremia (grades 3/4: 16% to 19%), hypophosphatemia (grades 3/4: ALL: 47%; MCL: 30%), increased uric acid (grades 3/4: 17% to 19%)
Gastrointestinal: Abdominal pain (17% to 19%), constipation (24% to 29%), decreased appetite (22% to 26%), diarrhea (28% to 32%; grades ≥3: 5% to 6%), mouth pain (ALL: 1%; MCL: 16%), nausea (35% to 41%; grades ≥3: 1%), vomiting (13% to 21%; grades ≥3: 3%)
Genitourinary: Decreased urine output (MCL: 11%)
Hematologic & oncologic: Anemia (grades 3/4: ALL: 77%; MCL: 55%), disorder of hemostatic components of blood (10% to 17%; grades ≥3: 2% to 5%), febrile neutropenia (ALL: 35%; MCL: 6%; grades 3/4: ALL: 35%), hemorrhage (7% to 13%; grades ≥3: ALL: 4%), hypogammaglobulinemia (9% to 16%; grades ≥3: 1%), leukopenia (grades 3/4: 95% to 99%), lymphocytopenia (grades 3/4: 86% to 96%), neutropenia (grades 3/4: 95% to 97%), thrombocytopenia (grades 3/4: ALL: 87%; MCL: 63%)
Hepatic: Increased direct serum bilirubin (ALL: 19%), increased serum alanine aminotransferase (grades 3/4: ALL: 31%; MCL: 15%), increased serum aspartate aminotransferase (grades 3/4: 15% to 23%)
Hypersensitivity: Cytokine release syndrome (91% to 92%)
Infection: Bacterial infection (13% to 15%), fungal infection (9% to 13%), infection (ALL: 28%; MCL: 43%, including severe infection), viral infection (ALL: 6%; MCL: 18%)
Nervous system: Agitation (12%), anxiety (12% to 16%), aphasia (MCL: 20%), chills (40% to 41%), confusion (26%), delirium (18%), dizziness (13% to 18%), encephalopathy (ALL: 63%; MCL: 51%), fatigue (ALL: 37%; MCL: 48%), headache (35% to 38%), insomnia (13% to 21%), motor dysfunction (MCL: 17%), myasthenia (ALL: 14%), neuropathy (MCL: 13%), neurotoxicity (81% to 87%, including immune effector cell-associated neurotoxicity syndrome [ICANS]), pain (13% to 17%), tremor (29% to 38%)
Neuromuscular & skeletal: Musculoskeletal pain (32% to 37%)
Renal: Kidney impairment (ALL: 6%; MCL: 18%)
Respiratory: Cough (ALL: 12%; MCL: 38%), dyspnea (ALL: 12%; MCL: 24%), hypoxia (31% to 40%), pleural effusion (ALL: 4%; MCL: 21%)
Miscellaneous: Fever (94% to 96%)
1% to 10%:
Cardiovascular: Bradycardia (MCL: 10%), heart failure (ALL: 4%), palpitations (ALL: 3%)
Dermatologic: Alopecia (ALL: 1%), dermal ulcer (ALL: 3%), hyperhidrosis (ALL: 1%), pressure ulcer (ALL: 3%), skin hyperpigmentation (ALL: 1%), skin lesion (ALL: 4%), xeroderma (ALL: 3%)
Endocrine & metabolic: Dehydration (5% to 6%)
Gastrointestinal: Dysphagia (4% to 10%), xerostomia (6% to 7%)
Hematologic & oncologic: Hemophagocytic lymphohistiocytosis (with macrophage activation syndrome: ALL: 4%; grade 3: 3%; grade 4: 1%), tumor lysis syndrome (ALL: 1%)
Hepatic: Hyperbilirubinemia (ALL: 10%)
Hypersensitivity: Hypersensitivity reaction (ALL: 1%)
Nervous system: Ataxia (5% to 7%), brain edema (ALL: 1%), cauda equina syndrome (ALL: 1%), cerebral herniation (ALL: 1%), increased intracranial pressure (MCL: 2%), myoclonus (ALL: 3%), paraplegia (ALL: 3%), peripheral neuropathy (ALL: 4%), seizure (5% to 8%)
Neuromuscular & skeletal: Monoplegia (ALL: 1%), muscle rigidity (ALL: 3%), muscle spasm (ALL: 4%)
Ophthalmic: Visual impairment (ALL: 9%)
Respiratory: Pneumonitis (ALL: 4%), pulmonary edema (4% to 6%), respiratory failure (6% to 9%)
Frequency not defined: Immunologic: Antibody development
Postmarketing:
Hematologic & oncologic: Hematologic malignancy (T-cell) (FDA Safety Communication 2023)
Hypersensitivity: Infusion-related reaction
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to brexucabtagene or any component of the formulation.
Concerns related to adverse effects:
• Cytokine release syndrome: Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving brexucabtagene autoleucel. CRS occurred in the majority of patients receiving brexucabtagene autoleucel; grade 3 and higher events were reported, including a fatal CRS event. The incidence of CRS (first occurrence) within the first 7 days after brexucabtagene autoleucel infusion was 83% in patients with mantle cell lymphoma and 90% in patients with acute lymphoblastic leukemia. The median time to onset of CRS was 3 to 5 days (range: 1 to 13 days); the median duration of CRS was 8 to 10 days (range: 1 to 63 days). Key manifestations of CRS include fever, hypotension, hypoxia, chills, tachycardia, headache, fatigue, and nausea; serious events also included dyspnea. Patients should seek immediate medical attention if signs or symptoms of CRS occur at any time.
• Cytopenias: Prolonged cytopenias may occur for several weeks after lymphodepleting chemotherapy and brexucabtagene autoleucel infusion. Unresolved (by day 30 following brexucabtagene autoleucel treatment) grade 3 and 4 cytopenias included thrombocytopenia, neutropenia, and anemia.
• Hemophagocytic lymphohistiocytosis/macrophage activation syndrome: Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) has occurred following brexucabtagene autoleucel infusion, including grade 3 or 4 events. The median time to onset of HLH/MAS was 8 days (range: 6 to 9 days); the median duration of HLH/MAS was 5 days (range: 2 to 8 days). All patients with HLH/MAS experienced concurrent CRS symptoms and neurologic events after brexucabtagene autoleucel infusion.
• Hepatitis B virus reactivation: Hepatitis B virus reactivation (sometimes resulting in fulminant hepatitis, hepatic failure, and death) may occur in patients treated with medications directed against B cells.
• Hypersensitivity: Serious hypersensitivity reactions, including anaphylaxis, may occur due to the dimethyl sulfoxide (DMSO) or residual gentamicin in brexucabtagene autoleucel.
• Hypogammaglobulinemia: Hypogammaglobulinemia and B-cell aplasia may occur in patients receiving brexucabtagene autoleucel.
• Infection: Serious infections (including life-threatening infections) have occurred. Infections occurred in ~50% of patients after brexucabtagene autoleucel infusion, including grades 3 and higher infections in 30% of patients. Bacterial, viral, and fungal infections were reported. Neutropenic fever has been observed after brexucabtagene autoleucel infusion and may occur concurrently with CRS. Life-threatening and fatal infections, including disseminated fungal infections and viral reactivation (eg, human herpes virus-6 encephalitis, progressive multifocal leukoencephalopathy) have been reported in immunosuppressed patients.
• Neurologic toxicities: Neurologic toxicities, including immune effector cell–associated neurotoxicity syndrome (ICANS) with fatal or life-threatening reactions, occurred in patients receiving brexucabtagene autoleucel. Neurologic events occurred in over 80% of patients receiving brexucabtagene autoleucel; grade 3 or higher events were observed. The median time to onset was 6 to 7 days (range: 1 to 51 days). The median duration of neurologic toxicities was 15 to 21 days (range: 1 to 454 days); neurologic toxicity resolved in close to 90% of patients, although persisted in some patients. The onset of neurologic events may be concurrent with CRS, following CRS resolution, or in the absence of CRS. The majority of patients experienced the first CRS or neurological events within the first 7 days after brexucabtagene autoleucel infusion. The most common neurologic events were encephalopathy, headache, tremor, confusion, aphasia, delirium, dizziness, anxiety, and agitation; serious events included encephalopathy, aphasia, confusion, and seizures. Due to the potential for neurologic events, including altered mental status or seizures, patients receiving brexucabtagene autoleucel are at risk for altered or decreased consciousness or coordination in the 8 weeks following administration; during this initial period, advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery.
• Secondary malignancy: Patients treated with brexucabtagene autoleucel may develop secondary malignancies. If a secondary malignancy occurs, contact the manufacturer (1-844-454-5483) to obtain patient sampling instructions for testing.
Concurrent drug therapy issues:
• Immunizations: Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during brexucabtagene autoleucel treatment, and until immune recovery following treatment. The safety of immunization with live viral vaccines during or following brexucabtagene autoleucel treatment has not been studied.
Dosage form specific issues:
• Dimethyl sulfoxide: Brexucabtagene autoleucel contains DMSO, which is associated with serious hypersensitivity reactions, including anaphylaxis.
• Universal precautions: Brexucabtagene autoleucel contains human blood cells that are genetically modified with replication-incompetent retroviral vector. Follow universal precautions and local biosafety guidelines for handling and disposal.
Other warnings/precautions:
• REMS program: Brexucabtagene autoleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the YESCARTA and TECARTUS REMS. Information is available at https://www.YescartaTecartusREMS.com or 1-844-454-5483.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Tecartus: One hundred million cells (1 ea); Two hundred million cells (1 ea) [contains albumin human]
No
Suspension (Tecartus Intravenous)
100000000CELLS (per each): $0.00
200000000CELLS (per each): $0.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Tecartus: Two hundred million cells (68 mL) [contains albumin human]
IV: For IV use only. Administer in a health care facility. For autologous use only. Coordinate the timing of administration with thawing (may be stored for up to 3 hours at room temperature after thawing); infusion start time may need to be adjusted based on thawing.
Prime the tubing with NS prior to infusion. Infuse entire contents of bag within 30 minutes either by gravity or a peristaltic pump (infusion bag volume is ~68 mL). A central line is preferred for infusion. Inspect the contents of the thawed infusion bag for visible cell clumps; if visible cell clumps remain, gently mix the contents of the bag (small clumps of cellular material should disperse with gentle manual mixing). Do not infuse if clumps are not dispersed, if the infusion bag is damaged or leaking, or if it otherwise appears to be compromised. Gently agitate the bag during infusion to prevent cell clumping. After completion of the infusion, rinse the tubing with NS at the same infusion rate to ensure complete cell product delivery. Do not use a leukodepleting filter. Apply universal precautions for product handling.
Prior to administration: Ensure tocilizumab and emergency equipment are available prior to infusion and during recovery period. Premedicate with acetaminophen and diphenhydramine (or another H1-antagonist) ~30 to 60 minutes prior to brexucabtagene autoleucel infusion. Avoid prophylactic systemic corticosteroids because they may interfere with the brexucabtagene autoleucel activity. Confirm patient identity and match to patient identifiers on the infusion cassette and bag.
Monitor patient daily at the health care facility for at least 7 days (mantle cell lymphoma) or 14 days (acute lymphoblastic leukemia) after cell infusion; patient should remain within proximity of the facility for at least 4 weeks after infusion.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Tecartus: https://www.gilead.com/-/media/files/pdfs/medicines/oncology/tecartus/tecartus_medguide.pdf
Acute lymphoblastic leukemia, B-cell precursor, relapsed or refractory: Treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults.
Mantle cell lymphoma, relapsed or refractory: Treatment of relapsed or refractory mantle cell lymphoma (MCL) in adults.
Brexucabtagene autoleucel may be confused with axicabtagene ciloleucel, betibeglogene autotemcel, brentuximab vedotin, ciltacabtagene autoleucel, elivaldogene autotemcel, exagamglogene autotemcel, idecabtagene vicleucel, lisocabtagene maraleucel, lovotibeglogene autotemcel, sipuleucel-T, tisagenlecleucel.
Tecartus may be confused with Yescarta.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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
Corticosteroids (Systemic): May enhance the adverse/toxic effect of CAR-T Cell Immunotherapy. Specifically, the severity and duration of neurologic toxicities may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of CAR-T Cell Immunotherapy. Management: Avoid use of corticosteroids as premedication before treatment with CAR-T cell immunotherapy agents. Corticosteroids are indicated and may be required for treatment of toxicities such as cytokine release syndrome or neurologic toxicity. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): CAR-T Cell Immunotherapy may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: The CDC recommends that CAR-T-cell recipients who received COVID-19 vaccine prior to or during treatment with CAR-T-cell therapy should be revaccinated with a primary mRNA vaccine series at least 3 months (12 weeks) after CAR-T-cell therapy. Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): CAR-T Cell Immunotherapy may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: The CDC recommends that CAR-T-cell recipients who received COVID-19 vaccine prior to or during treatment with CAR-T-cell therapy should be revaccinated with a primary vaccine series at least 3 months (12 weeks) after CAR-T-cell therapy. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect 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 enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect 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 enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 enhance the immunosuppressive effect 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
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to 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 enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect 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 enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect 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 combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Evaluate pregnancy status prior to use in patients who could become pregnant. Sexually active patients who could become pregnant should have a negative pregnancy test prior to initiating brexucabtagene autoleucel therapy. Consider contraception recommendations of concomitant therapy; the duration of effective contraception specific to brexucabtagene autoleucel treatment is not known.
Based on the mechanism of action, in utero exposure to brexucabtagene autoleucel may cause fetal harm.
It is not known if brexucabtagene autoleucel is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Screen for hepatitis B virus (HBV), hepatitis C virus, and HIV (prior to collection of cells for manufacturing). Monitor blood counts. Monitor immunoglobulin (IgG) levels after treatment. Evaluate pregnancy status prior to use in patients who could become pregnant.
Monitor for signs/symptoms of cytokine release syndrome (CRS) and neurological toxicities (including immune effector cell-associated neurotoxicity syndrome [ICANS]) for at least 4 weeks after treatment (monitor daily for at least the first 7 days [mantle cell lymphoma] or 14 days [acute lymphoblastic leukemia] after infusion at the health care facility; patients with ≥ grade 2 CRS or ≥ grade 2 neurologic toxicity/ICANS should be monitored with continuous cardiac telemetry and pulse oximetry). Monitor for hypersensitivity reactions and for signs/symptoms of infection, neutropenic fever, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Monitor (life-long) for secondary malignancies.
The American Society of Clinical Oncology HBV screening and management provisional clinical opinion (ASCO [Hwang 2020]) 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.
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Obtain baseline ECG, natriuretic peptides, and troponins; a baseline echocardiography is recommended in patients with preexisting cardiovascular disease; consider baseline echocardiography in all patients; for patients who develop ≥ grade 2 cytokine release syndrome, assess natriuretic peptides and troponins, and obtain echocardiography (ESC [Lyon 2022]). Refer to a cardiologist when clinically indicated.
Brexucabtagene autoleucel is a CD19-directed genetically modified autologous T cell immunotherapy in which a patient's T cells are reprogrammed with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells. The CAR is comprised of a murine single-chain antibody fragment which recognizes CD19 and is fused to CD28 and CD3 zeta. CD3 zeta is a critical component for initiating T cell activation and antitumor activity. After binding to CD19-expressing cells, the CD28 and CD3-zeta costimulatory domains activate downstream signaling cascades, which results in T cell activation, proliferation, acquisition of effector functions, and secretion of inflammatory cytokines and chemokines, leading to destruction of CD19-expressing cells. Brexucabtagene autoleucel is prepared from the patient's peripheral blood cells obtained via leukapheresis.
Note: In mantle cell lymphoma, the number of anti-CD19 chimeric antigen receptor (CAR) T cells in the blood was positively associated with objective response (complete remission or partial remission). The median peak anti-CD19 CAR T cell level in patients with mantle cell lymphoma who responded to therapy was 102.4 cells/mcL (range: 0.2 to 2,590 cells/mcL), compared to 12 cells/mcL (range: 0.2 to 1,364 cells/mcL) in nonresponders. The median peak anti-CD19 CAR T cell level in patients with acute lymphoblastic leukemia who had overall complete remission was 38.4 cells/mcL (range: 1.31 to 1,533.4 cells/mcL) and 424 cells/mcL compared to 0.5 cells/mcL (range: 0 to 183.5 cells/mcL) in patients who had noncomplete remission. The median AUC0-28 was also higher in patients with acute lymphoblastic leukemia who had overall complete remission, compared to patients who had noncomplete remission.
Onset: Mantle cell lymphoma: Median time to initial response: 1 month (range: 0.8 to 3.1 months); median time to complete response: 3 months (range: 0.9 to 9.3 months) (Wang 2020).
Duration: Anti-CD19 CAR T cells displayed an initial rapid expansion followed by a decline to near baseline levels by 3 months and 6 months (post-brexucabtagene autoleucel infusion) in mantle cell lymphoma and acute lymphoblastic leukemia, respectively.
Time to peak: Peak levels of anti-CD19 CAR T cells occurred within the first 15 days after infusion.
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