Lisocabtagene maraleucel

What is Lisocabtagene maraleucel?

• Lisocabtagene maraleucel (Breyanzi) is a CD19-directed genetically modified autologous T cell immunotherapy used for the treatment of adult patients with relapsed or refractory large B-cell lymphoma.

What are the uses of this medicine?

• Lisocabtagene maraleucel (Breyanzi) is a medicine used for the treatment of large B-cell lymphoma (including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B) in patients when at least 2 previous treatments have not worked or have stopped working.
• Breyanzi is a medicine made from your own white blood cells; the cells are genetically modified to recognize and attack your lymphoma cells.

Limitations of Use:

• Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.

How does this medicine work?

• Breyanzi is a CD19-directed genetically modified autologous cell immunotherapy administered as a defined composition to reduce variability in CD8-positive and CD4-positive T cell dose.
• Upon intravenous administration, lisocabtagene maraleucel is directed to and induce selective toxicity in CD19-expressing tumor cells.
• CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.
• Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T cells and can promote elimination of those cells through a cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) response. The 4-1BB costimulatory signaling domain enhances both proliferation of T cells and antitumor activity.

Who Should Not Use this medicine ?

Limitations of Use:

• Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.

What drug interactions can this medicine cause?

• Some commercial HIV nucleic acid tests may yield false-positive results in patients who have received Breyanzi.

Is this medicine FDA approved?

• Lisocabtagene maraleucel was approved for medical use in the United States in February 2021.

How should this medicine be used?

• Administer a lymphodepleting regimen of fludarabine and cyclophosphamide before infusion of Breyanzi.
• Verify the patient's identity prior to infusion.
• Premedicate with acetaminophen and an H1 antihistamine.
• Confirm availability of tocilizumab prior to infusion.

Recommended dosage:

• Dosing of Breyanzi is based on the number of chimeric antigen receptor (CAR)-positive viable T cells.
• The dose is 50 to 110 × 106 CAR-positive viable T cells (consisting of CD8 and CD4 components).

Administration:

• Administer Breyanzi in a certified healthcare facility.
• Breyanzi is made from your own white blood cells, so your blood will be collected by a process called "leukapheresis" (LOO-kuh-feh-REE-sis).
• It takes about 3-4 weeks from the time your cells are received at the manufacturing site and are available to be shipped back to your healthcare provider, but the time may vary.
• Before you get Breyanzi, you will get 3 days of chemotherapy to prepare your body.
• When your Breyanzi is ready, your healthcare provider will give it to you through a catheter (tube) placed into your vein (intravenous infusion). Breyanzi is given as infusions of 2 different cell types.
• You will receive infusions of one cell type, immediately followed by the other cell type.
• The time for infusion will vary, but will usually be less than 15 minutes for each of the 2 cell types.
• During the first week, you will be monitored daily by the facility where you received your treatment.
• You should plan to stay close to this location for at least 4 weeks after getting Breyanzi. Your healthcare provider will check to see that your treatment is working and help you with any side effects that may occur.
• You may be hospitalized for side effects and your healthcare provider will discharge you if your side effects are under control, and it is safe for you to leave the hospital.
• Your healthcare provider will want to do blood tests to follow your progress. It is important that you do have your blood tested. If you miss an appointment, call your healthcare provider as soon as possible to reschedule.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As suspension for intravenous infusion

This medicine is available in fallowing brand namesː

• Breyanzi

What side effects can this medication cause?

The most common side effects of this medicine include:

• fatigue
• difficulty breathing
• fever (100.4°F/38°C or higher)
• chills/shaking chills
• confusion
• difficulty speaking or slurred speech
• severe nausea, vomiting, diarrhea
• headache
• dizziness/lightheadedness
• fast or irregular heartbeat
• swelling

• Breyanzi can increase the risk of life-threatening infections that may lead to death.
• Breyanzi can lower one or more types of your blood cells (red blood cells, white blood cells, or platelets).

What special precautions should I follow?

• Allergic reactions may occur with the infusion of Breyanzi. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO). Monitor for hypersensitivity reactions during infusion.
• Severe infections, including life-threatening or fatal infections, have occurred in patients after Breyanzi infusion. Monitor patients for signs and symptoms of infection; treat appropriately.
• Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and Breyanzi infusion. Patients may exhibit Grade 3 or higher cytopenias for several weeks following Breyanzi infusion. Monitor complete blood counts.
• B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with Breyanzi. Monitor and consider immunoglobulin replacement therapy.
• The safety of immunization with live viral vaccines during or following Breyanzi treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy.
• Patients treated with Breyanzi may develop secondary malignancies. In the event that a secondary malignancy occurs after treatment with Breyanzi, contact Bristol-Myers Squibb at 1-888-805-4555.
• Do not drive, operate heavy machinery, or do other activities that could be dangerous if you are not mentally alert, for at least 8 weeks after you get Breyanzi. This is because the treatment can cause temporary memory and coordination problems, including sleepiness, confusion, dizziness, and seizures.
• Do not donate blood, organs, tissues, or cells for transplantation.
• Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with Breyanzi. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.
• Neurologic toxicities that were fatal or life-threatening, occurred following treatment with Breyanzi. . Monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after infusion; evaluate and treat promptly.
• Because of the risk of CRS and neurologic toxicities, Breyanzi is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Breyanzi REMS.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• There are no available data with Breyanzi use in pregnant women.
• Therefore, Breyanzi is not recommended for women who are pregnant, and pregnancy after Breyanzi infusion should be discussed with the treating physician.

Can this medicine be used in children?

• The safety and efficacy of Breyanzi have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

Active ingredients include:

• LISOCABTAGENE MARALEUCEL

Inactive ingredients include:

• DIMETHYL SULFOXIDE
• ALBUMIN HUMAN

Who manufactures and distributes this medicine?

• Manufactured by Juno Therapeutics Inc., a Bristol-Myers Squibb Company, Bothell, WA
• Breyanzi® is a trademark of Juno Therapeutics, Inc., a Bristol-Myers Squibb Company.

What should I know about storage and disposal of this medication?

• Store vials in the vapor phase of liquid nitrogen (less than or equal to minus 130°C) in a temperature-monitored system.
• Thaw Breyanzi prior to infusion.

• Dailymed label info on Lisocabtagene maraleucel
• FDA Lisocabtagene maraleucel