Brexucabtagene Autoleucel

Brexucabtagene Autoleucel is a prescription medication indicated for relapsed or refractory mantle cell lymphoma (MCL). Brexucabtagene Autoleucel is also indicated for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

• Brexucabtagene Autoleucel is available under the following different brand names: Tecartus.

Common side effects of Brexucabtagene Autoleucel include:

• fever
• cytokine release syndrome
• low blood pressure (hypotension)
• encephalopathy
• fatigue
• fast heart rate
• irregular heartbeats
• infection
• chills
• low blood oxygen (hypoxia)
• cough
• tremor
• musculoskeletal pain
• headache
• nausea
• fluid retention (edema)
• motor dysfunction
• constipation
• diarrhea
• decreased appetite
• shortness of breath
• rash
• insomnia
• fluid around the lungs (pleural effusion)
• problems speaking and understanding language (aphasia)

Serious side effects of Brexucabtagene Autoleucel include:

• severe drowsiness
• trouble speaking or writing
• trouble with daily activities
• seizure
• severe ongoing nausea, vomiting, or diarrhea
• low blood cell counts--fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands, and feet, feeling light-headed or short of breath
• kidney problems--little or no urination, swelling in the feet or ankles, feeling tired or short of breath
• fluid build-up in or around the lungs--pain while breathing, feeling short of breath while lying down, wheezing, gasping for breath, cough with foamy mucus, cold and clammy skin, anxiety, rapid heartbeats

Rare side effects of Brexucabtagene 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

• Single-dose units contain specific amounts of T cells depending on the patient’s body weight that are suspended in a patient-specific infusion bag
• 2x 106 CAR-positive viable T cells/kg of body weight, with a maximum of 2x 108 CAR-positive viable T cells in approximately 68 mL

Mantle cell lymphoma

Adult dosage

• Lymphodepleting chemotherapy
  • 3 doses of fludarabine and cyclophosphamide infused IV on the fifth, fourth, and third day before infusion of brexucabtagene Autoleucel
  • Fludarabine 30 mg/m2 IV once a day for 3 days
  • Cyclophosphamide 500 mg/m2 IV once a day for 3 days starting with the first dose of fludarabine

Brexucabtagene Autoleucel IV infusion

• For autologous use only, administer after completing lymphodepleting chemotherapy
• Dose based on the number of chimeric antigen receptor (CAR)-positive viable T cells
• Target dose is 2x 106 CAR-positive viable T cells/kg body weight, not to exceed 2x 108 CAR-positive viable T cells
• Administer autologously prepared, weight-based IV infusion for individual patients within 30 minutes by either gravity or peristaltic pump
• Do not use a leukocyte-depleting filter

Acute lymphoblastic leukemia

Adult dosage

• Lymphodepleting chemotherapy
  • Fludarabine 25 mg/m2 IV over 30 minutes on the fourth, third, and second day before infusion of brexucabtagene Autoleucel
  • Cyclophosphamide 900 mg/m2 IV over 60 min on the second day before infusion Brexucabtagene autoleuce

Brexucabtagene Autoleucel IV infusion

• For autologous use only; administer after completing lymphodepleting chemotherapy
• Dose based on the number of chimeric antigen receptor (CAR)-positive viable T cells
• Target dose is 1x 106 CAR-positive viable T cells/kg body weight, not to exceed 1x 108 CAR-positive viable T cells

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, healthcare provider, or pharmacist first.

• Brexucabtagene Autoleucel has severe interactions with no other drugs
• Brexucabtagene Autoleucel has serious interactions with at least 197 other drugs
• Brexucabtagene Autoleucel has moderate interactions with no other drugs
• Brexucabtagene Autoleucel has minor interactions with no 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

• None

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment in most patients 
• Available only through a restricted access program
• Allergic reactions may occur during infusion; serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide or residual gentamicin in the product
• Viral reactivation can occur; hepatitis B virus (HBV) reactivation can result in fulminant hepatitis, hepatic failure, and death; perform screening for HBV, hepatitis C virus, and HIV following clinical guidelines before collection of cells for manufacturing
• Prolonged cytopenias may occur and last for several weeks following lymphodepleting chemotherapy and Brexucabtagene Autoleucel infusion; monitor blood cell counts
• B-cell aplasia and hypogammaglobulinemia can occur; monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement standard guidelines
• Secondary malignancies may develop; monitor patient life-long for secondary malignancies
• Hemophagocytic lymph histiocytosis/macrophage activation syndrome (HLH/MAS), including life-threatening reactions reported; patients with HLH/MAS reported to have CRS symptoms and neurologic events after infusion; administer HLH/MAS treatment per institutional standards
• Infection risk
  • Serious infections, including life-threatening or fatal infections, reported; before administering, infection prophylaxis for neutropenia should follow local guidelines; monitor for signs and symptoms of infection after treatment and treat appropriately
  • Life-threatening and fatal opportunistic infections reported in immunosuppressed patients; consider the possibility of rare infectious etiologies (eg, fungal and viral infections such as HHV-6 and progressive multifocal leukoencephalopathy) in patients with neurologic events; perform appropriate diagnostic procedures
  • Viral reactivation can occur; hepatitis B virus (HBV) reactivation can result in fulminant hepatitis, hepatic failure, and death; perform screening for HBV, hepatitis C virus, and HIV following clinical guidelines before collection of cells for manufacturing
• Neurologic effects
  • Neurological toxicities, which may be severe or life-threatening, can occur following treatment
  • Owing to the potential for neurological events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following treatment; advise patients to refrain from driving and engaging in hazardous occupations or activities
• FDA MedWatch alert
  • November 28, 2023: FDA has received reports of T-cell malignancies, including chimeric antigen receptor CAR-positive lymphoma, in patients who received treatment with BCMA- or CD19-directed autologous CAR-T cell immunotherapies
  • Reports came from clinical trials and/or postmarketing adverse event data sources
  • FDA determined the risk of T-cell malignancies applies to all currently approved BCMA-directed and CD19-directed genetically modified autologous CAR-T cell immunotherapies
  • Although overall benefits continue to outweigh their potential risks for 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
  • Monitor patients and clinical trial participants receiving treatment for life-long new malignancies
  • If new malignancy occurs following treatment, contact the manufacturer to report the event and obtain instructions on the collection of patient samples for testing for the presence of CAR transgene
• Immunization with live viral vaccines
  • Safety of immunization with live viral vaccines during or following treatment has not been studied
  • Vaccination with live-virus vaccines is not recommended for at least 6 weeks before the start of lymphodepleting chemotherapy, during Brexucabtagene Autoleucel treatment, and until immune recovery afterwards

Pregnancy and Lactation

• Data are not available in pregnant women
• No animal reproductive and developmental toxicity studies have been conducted
• Based on the mechanism of action, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell lymphocytopenia
• Therefore, brexucabtagene Autoleucel is not recommended during pregnancy, and pregnancy after infusion should be discussed with the treating physician
• Verify the pregnancy status of women with reproductive potential; sexually active women of reproductive potential should have a pregnancy test before starting treatment
• Contraception
  • See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive lymphodepleting chemotherapy
  • Limited exposure data available concerning the duration of contraception following treatment
• Latcation
  • Unknown if distributed in human breast milk
  • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or the underlying maternal condition