Breyanzi (lisocabtagene maraleucel) for relapsed or refractory marginal zone lymphoma

Initial US Approval:

2021

Key Clinical Studies:

TRANSCEND FL-MZL Cohort (NCT04245839)

Drug Class/Description:

CD19-directed genetically modified autologous T cell immunotherapy

Indications and Usage:

BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

• adult patients with large B-cell lymphoma (LBCL), 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, who have:
  • refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
  • refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
  • relapsed or refractory disease after 2 or more lines of systemic therapy.

Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.

• adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
• adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). 
• adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor. 
• adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 2 prior lines of systemic therapy.

Dosage and Administration:

For autologous use only. For intravenous use only.

• Do NOT use a leukodepleting filter.
• 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.
• Dosing of BREYANZI is based on the number of chimeric antigen receptor (CAR)-positive viable T cells.

For LBCL:

• after one line of therapy, the dose is 90 to 110 × 10⁶ CAR-positive viable T cells.
• after two or more lines of therapy, the dose is 50 to 110 × 10⁶ CAR-positive viable T cells.

For CLL/SLL, FL, MCL and MZL:

• the dose is 90 to 110 × 10⁶ CAR-positive viable T cells. 

Dosage Forms and Strengths:

• BREYANZI is a cell suspension for infusion.
• A single dose of BREYANZI consists of 1:1 CAR-positive viable T cells of the CD8 and CD4 components, with each component supplied separately in one to four single-dose 5 mL vials. Each mL contains ≥ 1.5 × 10⁶ to 70 × 10⁶ CAR-positive viable T cells.

Contraindications:

None.

Warnings and Precautions:

• Hypersensitivity Reactions: Monitor for hypersensitivity reactions during infusion. 
• Serious Infections: Monitor patients for signs and symptoms of infection; treat appropriately. 
• Prolonged Cytopenias: Patients may exhibit Grade 3 or higher cytopenias for several weeks following BREYANZI infusion. Monitor complete blood counts. 
• Hypogammaglobulinemia: Monitor and consider immunoglobulin replacement therapy. 
• Secondary Malignancies: T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI.

Adverse Reactions:

The most common adverse reactions (incidence ≥ 30%) in:

• LBCL are fever, CRS, fatigue, musculoskeletal pain, and nausea. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease.
• CLL/SLL are CRS, encephalopathy, fatigue, musculoskeletal pain, nausea, edema and diarrhea. The most common Grade 3-4 laboratory abnormalities include neutrophil count decrease, white blood cell decrease, hemoglobin decrease, platelet count decrease, and lymphocyte count decrease. 
• FL are CRS. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decreased, neutrophil count decreased, and white blood cell decreased.
• MCL are CRS, fatigue, musculoskeletal pain, and encephalopathy. The most common Grade 3-4 laboratory abnormalities include neutrophil count decrease, white blood cell decrease, and platelet count decrease. 
• MZL are CRS. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decreased, neutrophil count decreased, and white blood cell decreased.

Adapted From:

https://packageinserts.bms.com/pi/pi_breyanzi.pdf

 

Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.