General Information

Breyanzi (lisocabtagene maraleucel; liso-cel) is a CD19-directed chimeric antigen receptor (CAR) T cell therapy. 

Breyanzi is specifically indicated for:

• the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, 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
• 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
  • Refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant (HSCT) due to comorbidities or age.

Breyanzi is supplied as a suspension for intravenous administration. A single dose of Breyanzi contains 50 to 110 × 106 CAR-positive viable T cells (consisting 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 vial.

Breyanzi is for autologous use only. The patient’s identity must match the patient identifiers on the Breyanzi cartons, vials and syringe labels. Do not infuse Breyanzi if the information on the patient-specific labels does not match the intended patient.

• Preparing the Patient for Breyanzi: Confirm the availability of Breyanzi before starting lymphodepleting chemotherapy.
• Pretreatment: Administer the lymphodepleting chemotherapy regimen before infusion of Breyanzi: fludarabine 30 mg/m2 /day intravenously (IV), and cyclophosphamide 300 mg/m2 /day IV for 3 days. See the prescribing information for fludarabine and cyclophosphamide for information on dose adjustment in renal impairment. Infuse Breyanzi 2 to 7 days after completion of lymphodepleting chemotherapy. Delay the infusion of Breyanzi if the patient has unresolved serious adverse events from preceding chemotherapies, active uncontrolled infection, or active graft-versus-host disease (GVHD).
• Premedication: To minimize the risk of infusion reactions, pre-medicate the patient with acetaminophen (650 mg orally) and diphenhydramine (25-50 mg, IV or orally), or another H1-antihistamine, 30 to 60 minutes prior to treatment with Breyanzi. Avoid prophylactic use of systemic corticosteroids, as they may interfere with the activity of Breyanzi.

Please refer to the drug label for specific directions in the preparation and infusion of Breyanzi administration. 

Mechanism of Action

Breyanzi (lisocabtagene maraleucel; liso-cel) 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. The CAR is comprised of an FMC63 monoclonal antibody-derived single chain variable fragment (scFv), IgG4 hinge region, CD28 transmembrane domain, 4-1BB (CD137) costimulatory domain, and CD3 zeta activation domain. CD3 zeta signaling is critical for initiating activation and antitumor activity, while 4-1BB (CD137) signaling enhances the expansion T cell and persistence of BREYANZI. CAR binding to CD19 expressed on the cell surface of tumor and normal B cells induces activation and proliferation of CAR T cells, release of pro-inflammatory cytokines, and cytotoxic killing of target cells.

Side Effects

Adverse effects associated with the use of Breyanzi may include, but are not limited to, the following:

• fatigue
• cytokine release syndrome
• musculoskeletal pain
• nausea
• headache
• encephalopathy
• infections (pathogen unspecified)
• decreased appetite
• diarrhea
• hypotension
• tachycardia
• dizziness
• cough
• constipation
• abdominal pain
• vomiting
• edema

The Breyanzi drug label comes with the following Black Box Warning: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES: Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Breyanzi. Do not administer Breyanzi to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids. Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Breyanzi, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with Breyanzi. Provide supportive care and/or corticosteroids as needed. Breyanzi is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Breyanzi REMS.

Clinical Trial Results

The FDA approval of Breyanzi was based on data from the TRANSCEND NHL 001, an open-label, multicenter, single-arm trial in adult patients with relapsed or refractory large B-cell non-Hodgkin lymphoma after at least 2 lines of therapy. In the study, 192 patients were treated with Breyanzi at the dose of 50 to 110 x 106 CAR-positive viable T cells and evaluated for efficacy. Of these patients, 73% achieved a response, including 54% who had minimal or no detectable lymphoma remaining following treatment and 19% who achieved a partial response. Median duration of response was 16.7 months in all responders, and for patients who achieved a CR, median duration of response was not reached; for patients with a best response of PR, median duration of response was 1.4 months. Of 104 patients treated with Breyanzi who achieved a best overall response of CR, 65% had remission lasting at least six months and 62% had remission lasting at least nine months.

The approval of the expanded first-line indications for Breyanzi is based on results from the pivotal Phase 3 TRANSFORM study in which adults with LBCL that was primary refractory or relapsed within 12 months of front-line therapy were randomized to receive Breyanzi or standard therapy consisting of salvage immunochemotherapy, and if responsive, high-dose chemotherapy and HSCT. The trial included patients with diverse histologic subtypes and high-risk features, and offered a patient-centric design, allowing for bridging immunochemotherapy in the Breyanziarm for disease control. Results from the TRANSFORM study showed, Breyanzi (n=92) more than quadrupled median EFS compared to standard therapy (n=92) (10.1 months vs. 2.3 months. The majority of patients achieved a CR with Breyanzi compared to less than half with standard therapy (66% vs. 39%) with median duration of CR not reached in the Breyanzi arm. Results also showed Breyanzi more than doubled PFS versus standard therapy (median PFS: 14.8 months vs. 5.7 months. In the study, nearly all patients (97%) in the Breyanzi arm received treatment versus less than half (47%) of patients who completed high-dose chemotherapy and autologous HSCT in the standard therapy arm.