Lisocabtagene maraleucel (Breyanzi) — Clinical FAQs

Question 1

What is Lisocabtagene maraleucel FDA-approved to treat?

Accepted Answer

Lisocabtagene maraleucel is FDA-approved for the following oncology indications: 1. Relapsed or refractory large B-cell lymphoma (LBCL) after ≥2 prior lines of systemic therapy, including DLBCL not otherwise specified, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B (approved February 2021; TRANSCEND NHL 001 trial) 2. Relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) after ≥2 prior lines including a BTK inhibitor and BCL-2 inhibitor (approved March 2024; TRANSCEND CLL 004 trial) 3. Relapsed or refractory follicular lymphoma (FL) after ≥3 prior lines of systemic therapy (approved June 2023; TRANSCEND FL trial) 4. Relapsed or refractory mantle cell lymphoma (MCL) after ≥2 prior lines of systemic therapy including a BTK inhibitor (approved June 2024; TRANSCEND MCL trial) 5. Relapsed or refractory LBCL after ≥1 prior line of chemoimmunotherapy when not eligible for autologous stem cell transplant (approved June 2022; PILOT trial).

Question 2

How does Lisocabtagene maraleucel work (mechanism of action)?

Accepted Answer

Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy composed of separate CD4+ and CD8+ T-cell components administered in a defined ratio. Each T cell is transduced with a lentiviral vector encoding a CAR construct comprising a CD19-specific single-chain variable fragment (scFv), a 4-1BB (CD137) costimulatory domain, and a CD3ζ signaling domain. Upon engagement with CD19-expressing B-cell malignancy cells, the CAR activates intracellular signaling cascades leading to T-cell activation, cytokine secretion, and direct cytolytic killing of target cells. The 4-1BB costimulatory domain promotes T-cell persistence and a memory phenotype, potentially contributing to more durable remissions compared to CD28-based constructs.

Question 3

How is Lisocabtagene maraleucel administered?

Accepted Answer

Lisocabtagene maraleucel is administered Intravenous (IV). Liso-cel is administered as a single IV infusion following lymphodepleting chemotherapy with fludarabine 30 mg/m²/day IV and cyclophosphamide 300 mg/m²/day IV on days -5, -4, and -3 prior to infusion (day 0).

Question 4

What are the most common side effects of Lisocabtagene maraleucel?

Accepted Answer

The most commonly reported side effects of Lisocabtagene maraleucel (≥10% incidence) include: CRS (any grade, ~42–46%), Fatigue, Musculoskeletal pain, Nausea, Headache and others (14 total). Consult your oncologist for complete prescribing information.

Question 5

Does Lisocabtagene maraleucel have a black box warning?

Accepted Answer

Yes. Lisocabtagene maraleucel carries FDA black box warning(s) regarding: 1. Cytokine release syndrome (CRS): life-threatening or fatal CRS occurred; do not administer to patients with active uncontrolled infection or inflammatory disorders; manage with tocilizumab and/or corticosteroids 2. Neurological toxicities (ICANS — immune effector cell-associated neurotoxicity syndrome): severe or life-threatening including encephalopathy, seizures, cerebral edema, aphasia, and delirium 3. HLH/macrophage activation syndrome (MAS): life-threatening cases reported, often associated with CRS; evaluate and treat accordingly 4. Prolonged cytopenias: patients may exhibit delayed and prolonged severe cytopenias (neutropenia, thrombocytopenia, anemia) following lymphodepletion and liso-cel infusion 5. Secondary T-cell malignancies including CAR-positive T-cell lymphomas: reported post-treatment; may present as rapidly progressive disease; new or worsening symptoms post-treatment require evaluation 6. Available only through a REMS program (Breyanzi REMS) due to risk of CRS and neurological toxicities

Question 6

Is Lisocabtagene maraleucel safe during pregnancy?

Accepted Answer

Lisocabtagene maraleucel pregnancy safety: No adequate data in pregnant women. Based on mechanism of action (potent immune activation and lymphodepletion), significant risk of fetal harm is expected. Advise females of reproductive potential to use effective contraception. Fludarabine and cyclophosphamide used in lymphodepletion conditioning are known teratogens (Category D). Patients should not become pregnant until hematologic and immune recovery is confirmed.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

lisocabtagene maraleucel — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms