Breyanzi for treating large B-cell and other lymphomas in adults

Breyanzi is an intravenous autologous immunotherapy consisting of genetically modified T cells designed to target CD19-positive B-cell cancers. It is used primarily in adults with various types of relapsed or refractory large B-cell lymphoma and other specified lymphomas after prior treatment with chemotherapy or targeted therapies.

Breyanzi is approved for the treatment of adult patients with:

• Large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have refractory disease to first-line chemoimmunotherapy, relapse within or after 12 months of first-line treatment and are ineligible for stem cell transplant due to age or comorbidities, or relapsed/refractory disease after two or more lines of systemic therapy.
• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that is relapsed or refractory after at least two prior lines of therapy including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor (accelerated approval).
• Relapsed or refractory follicular lymphoma (FL) after two or more prior systemic therapies.
• Relapsed or refractory mantle cell lymphoma (MCL) after at least two prior therapies, including a BTK inhibitor.
• Relapsed or refractory marginal zone lymphoma (MZL) after at least two prior lines of therapy.

Limitations: Not indicated for primary central nervous system lymphoma.

Lisocabtagene maraleucel

Breyanzi works by using the patient’s own T cells that have been genetically engineered to express a chimeric antigen receptor (CAR) targeting the CD19 protein on B cells. These CAR T cells recognize and kill cancerous B cells expressing CD19, helping to control or eliminate lymphoma.

Breyanzi is given as a single intravenous infusion of autologous CAR-positive viable T cells consisting of two components (CD8 and CD4) in a 1:1 ratio. Dosing is based on the number of CAR-positive T cells.

• For LBCL after one line of therapy: 90 to 110 million CAR-positive viable T cells.
• For LBCL after two or more lines of therapy: 50 to 110 million CAR-positive viable T cells.
• For CLL/SLL, FL, MCL, and MZL: 90 to 110 million CAR-positive viable T cells.

Before infusion, patients receive a lymphodepleting chemotherapy regimen of fludarabine 30 mg/m2/day IV and cyclophosphamide 300 mg/m2/day IV for 3 days. Breyanzi is then infused 2 to 7 days following chemotherapy.

Premedication with acetaminophen (650 mg orally) and an H1 antihistamine (e.g., diphenhydramine 25-50 mg IV or orally) is recommended about 30 to 60 minutes before treatment to reduce infusion reactions. Prophylactic systemic corticosteroids are avoided as they may reduce Breyanzi activity.

Breyanzi must be administered soon after thawing, within 2 hours, and requires careful handling with identity verification to match the patient.

There are no explicit contraindications listed in the labeling, but Breyanzi must not be administered to patients with active infections or active graft-versus-host disease.

Serious risks include:

• Cytokine release syndrome (CRS): Can be life-threatening or fatal. BREYANZI must not be given to patients with active infections or inflammatory disorders. Prompt recognition and treatment with tocilizumab (an IL-6 receptor antagonist) with or without corticosteroids is critical.
• Neurologic toxicities: Severe or fatal neurologic events have occurred, sometimes independent of CRS or after CRS resolution. Close monitoring and supportive care including corticosteroids should be provided as needed.
• Secondary hematological malignancies: Cases of T-cell malignancies have been reported after treatment with CAR T-cell therapies including BREYANZI.

Common adverse reactions include cytokine release syndrome (CRS) and neurologic toxicities, which may be severe or life-threatening.

Other potential toxicities include infusion reactions, infections, cytopenias, and secondary malignancies.

Patients should be closely monitored, especially during the first week after infusion.

The label does not provide specific drug interaction data for Breyanzi; however, concurrent use with immunosuppressive agents, particularly systemic corticosteroids, may reduce the effectiveness of the therapy.

The label does not describe specific overdose manifestations or management.

Breyanzi is shipped and stored in the vapor phase of liquid nitrogen. If the patient is not ready for infusion before the shipper expires, it should be transferred to appropriate onsite vapor phase liquid nitrogen storage if the facility is qualified. Otherwise, arrangements for return shipment must be made.