Rx Road Map: Lisocabtagene Maraleucel for Mantle Cell Lymphoma

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Whom Is This Drug Approved for?

Lisocabtagene maraleucel (Breyanzi; liso-cel) CAR T-cell therapy is indicated for the treatment of adult patients with relapsed/refractory mantle cell lymphoma (MCL) who have previously received 2 or more lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor.^1-3 The FDA approved liso-cel for this indication on May 30, 2024.^2,4

Liso-cel is also FDA approved for adult patients with other B-cell malignancies, as follows^1-3:

1. Large B-cell lymphoma (LBCL)
   1. Refractory to first-line chemoimmunotherapy
   2. Relapsed within 12 months of first-line chemoimmunotherapy
   3. Relapsed/refractory to first-line chemoimmunotherapy and not eligible for hematopoietic stem cell transplantation
   4. Relapsed/refractory following 2 or more lines of treatment
2. Chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) refractory to 2 or more lines of treatment, including a BTK inhibitor and a BCL-2 inhibitor
3. Follicular lymphoma refractory to 2 or more lines of treatment

What Efficacy Data Back It Up?

The safety and efficacy of liso-cel were evaluated in the TRANSCEND-MCL (NCT02631044) trial, a multicenter, open-label, single-arm clinical trial. Participants were adult patients with relapsed/refractory MCL who had previously received at least 2 prior lines of therapy, including a BTK inhibitor, an anti-CD20 agent, and an alkylating agent. The trial efficacy analysis included a 68 patients. Following the outcomes of the trial, the overall response rate (ORR), defined as a percentage of patients with either complete response (CR) or partial response (PR), was 85.3% (95% CI, 74.6%-92.7%), while the CR rate (CRR) was 67.6% (95% CI, 55.2%-78.5%). After a median follow-up time of 22.2 months, the median duration of response (DOR) was found to be 13.3 months (95% CI, 6.0-23.3).

How Does Liso-Cel Work?

Liso-cel is a CD19-directed genetically modified autologous T-cell immunotherapy.¹ The patient undergoes collection of their own T cells, which are sent to the manufacturer for genetic modification.² These cells are modified via a lentiviral vector to express a chimeric antigen receptor (CAR). This CAR can specifically bind CD19 receptors on cancerous B cells, thus allowing these modified T cells to target and destroy cancerous B cells directly.^1,4

How It’s Administered

Prior to the administration of liso-cel, the patient will complete lymphodepleting chemotherapy (LDC) with fludarabine (30mg/m² daily intravenously, IV) and cyclophosphamide (300mg/m² daily, IV) for 3 consecutive days. Liso-cel will then be infused within 2 to 7 days of completing LDC. Liso-cel may be infused only at a Risk Evaluation and Mitigation Strategy (REMS)–certified health care facility; this can be in an outpatient or inpatient setting, per the institution’s standard-of-practice guidelines.

Liso-cel will be shipped directly from the manufacturer to the designated institution’s cellular therapy laboratory or clinical pharmacy. It will arrive in the vapor phase of a liquid nitrogen shipper. Once the patient’s infusion time is confirmed, the cellular therapy laboratory will begin the thawing process, which must be completed and the cells infused within 2 hours.

To minimize the risk of an infusion reaction, patients will be premedicated with acetaminophen and diphenhydramine or another H1-antihistamine prior to receiving liso-cel. Liso-cel is administered intravenously through a central venous catheter using tubing without a leukodepleting filter.

The CD8 component is infused first, followed by the CD4 component, per package insert instructions. Patients are monitored daily for at least 7 days following liso-cel infusion at a REMS-certified health care facility for signs and symptoms of cytokine release syndrome (CRS) and neurologic toxicities.^1,3,4

Dosing

The recommended dose of liso-cel for patients with MCL is 90 to 110 x 10⁶ CAR-positive viable T cells, consisting of a 1:1 ratio of CD4 and CD8 components.^1,4

How to Manage Associated Adverse Events

The TRANSCEND study reported associated adverse events (AEs), with the MCL cohort specifically evaluating the safety of liso-cel in patients with MCL. The most common associated AEs, occurring in 20% or more of patients, included cytokine release syndrome (CRS), fatigue, decreased appetite, edema, headache, encephalopathy, and musculoskeletal pain. Serious AEs occurred in 53% of patients in the MCL cohort, with fatal AEs occurring in 4.5% of patients.^1,3,4

The most dangerous AEs following treatment with liso-cel are described below. The most common serious AE as noted in the TRANSCEND-MCL cohort was CRS, which occurred in 61% of patients, 1.1% of whom experienced grade 3 or higher CRS.^1,3,4

• Cytokine release syndrome
  • CRS is identified and graded based on clinical presentation and response to supportive care and interventions. The most common symptoms of CRS are fever, hypotension, and hypoxia.^1,3,4
  • Treatment of CRS includes supportive care (antipyretics, supplemental oxygen, IV fluids) and tocilizumab (repeated every 8 hours as needed, not to exceed maximum of 4 total doses), with or without the addition of corticosteroids, per the American Society for Transplantation and Cellular Therapy (ASTCT) grading guidelines and treatment algorithm listed in the package insert.^1,3-5
  • Confirm tocilizumab availability (2 doses per patient) prior to the infusion of liso-cel.^1,3,4
• Neurologic toxicity
  • The most common neurologic toxicities (≥5%) include tremor, expressive aphasia, delirium, headache, and encephalopathy.^1,3,4
  • Serious and potentially fatal neurologic toxicities were also reported, including immune effector cell–associated neurotoxicity syndrome, seizures, and cerebral edema.^1,3,4
  • Treatment for neurologic toxicity includes corticosteroids per the ASTCT grading guidelines and treatment algorithm listed in the package insert.^1,3-5
  • Prophylaxis with antiseizure medications (such as levetiracetam) is recommended beginning prior to the infusion of liso-cel.^1,3,4
• Serious infections
  • Infections of an unspecified pathogen, including sepsis, occurred in 16% of patients in the TRANSCEND MCL-cohort. Upper respiratory infections occurred in 13% of patients in the MCL cohort.^1,3,4
• Prolonged cytopenias
  • Grade 3 or 4 cytopenias occurred in 10% or more of patients in the TRANSCEND-MCL cohort, including decreased lymphocyte count (89%), decreased neutrophil count (85%), thrombocytopenia (39%), and decreased hemoglobin (33%).^1,3,4
• Hypogammaglobulinemia
  • B-cell aplasia can occur in patients following treatment with liso-cel. Patients should be monitored for hypogammaglobulinemia (defined as immunoglobulin G level below 500 mg/dL) with IV immunoglobulin replacement as clinically indicated.^1,3,4
• Secondary T-cell malignancies
  • Patients who have received liso-cel or other CAR T-cell therapies may develop a secondary T-cell malignancy. Mature T-cell malignancies may present as early as weeks following liso-cel infusion. Patients should undergo lifelong monitoring for secondary T-cell malignancies.^1,3,4

What to Inform Patients About to Start Treatment

Patients should be counseled regarding the possible AEs listed above. Due to the prolonged cytopenias and risk of infection as described above, patients should be counseled on infectious precautions. Patients should be advised to reside in proximity (ie, approximately within 1 hour) to a REMS-certified health care facility for at least 4 weeks following liso-cel administration, and have a designated caregiver present for 24-hour care. Due to the possibility of neurologic toxicities, patients should be advised not to drive or operate heavy machinery for at least 8 weeks following liso-cel administration.^1,4

Advice for Nurses Who Administer Liso-Cel

Liso-cel CAR T-cell therapy has a wide range of possible adverse effects requiring close monitoring and prompt recognition of symptoms. Nurses and providers caring for patients after liso-cel should be familiar with and pay particular attention to the symptoms of CRS and neurologic toxicities.

How to Safely Handle This Drug

Liso-cel contains human blood cells that have been genetically modified with a lentiviral vector. Universal precautions and institutional biosafety guidelines should be followed for handling and disposal to prevent the potential transmission of infectious diseases.^1,4

References

1. Breyanzi (lisocabtagene maraleucel) [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2024.
2. Breyanzi CAR T Cell Therapy for 3L+ R/R MCL: For HCPs. Breyanzi HCP. 2024. Accessed February 17, 2025. https://www.breyanzihcp.com/mcl
3. Breyanzi (lisocabtagene maraleucel). FDA. March 4, 2021. Accessed February 17, 2025. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/breyanzi-lisocabtagene-maraleucel
4. FDA approves lisocabtagene maraleucel for relapsed or refractory mantle cell lymphoma. FDA. May 30, 2024. Accessed March 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lisocabtagene-maraleucel-relapsed-or-refractory-mantle-cell-lymphoma.
5. Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758