Rx Road Map: Lisocabtagene Maraleucel in Follicular Lymphoma

For Which Patients With Follicular Lymphoma Is Lisocabtagene Maraleucel Approved?

On May 15, 2024, the FDA approved lisocabtagene maraleucel (liso-cel; Breyanzi) for adults with relapsed or refractory follicular lymphoma who have received 2 or more lines of systemic therapy.¹

What Efficacy Data Back It Up?

Approval was based on efficacy data from the phase 2 open-label, multicenter TRANSCEND-FL trial (NCT04245839), which measured overall response rate (ORR) and duration of response (DOR) as determined by an independent review committee. The ORR was 95.7% (95% CI, 89.5%-98.8%), and at a median follow-up of 16.8 months (95% CI, 16.3-17.0), the median DOR was not reached (NR; 95% CI, 18.04-NR).

How It Works

Liso-cel is a form of personalized therapy where a patient’s own T cells are genetically engineered to express a chimeric antigen receptor (CAR) that targets CD19, a protein found on the surface of tumor cells and normal B cells. Binding to CD19 triggers activation and expansion of the CAR T cells, leading to cytotoxic destruction of the target cells.^2,3

How It’s Administered

Liso-cel is administered as a single intravenous (IV) infusion consisting of 2 separate cell components (CD8 and CD4) that are divided into 1 to 4 single-dose vials or syringes.

In the week prior to the planned liso-cel infusion, patients receive lymphodepleting chemotherapy consisting of fludarabine 30 mg/m² per day and cyclophosphamide 300 mg/m² per day, both administered intravenously for 3 consecutive days. Liso-cel is then infused from 2 to 7 days after completing chemotherapy in a certified health care facility.^3,4

On the day of infusion, premedication is required due to a high risk of infusion-related reactions (IRR). Patients receive acetaminophen at 650 mg orally and diphenhydramine at 25 to 50 mg IV or orally (or another H1-antihistamine) 30 to 60 minutes prior to the planned infusion. Corticosteroids are not used as a premedication as they could interfere with the CAR T.⁴ Ensure emergency equipment and tocilizumab are available prior to cell infusion in the event of IRR.

Flush the infusion tubing with normal saline (NS) prior to and after each CD8 or CD4 component administration. Administer the entire volume of the CD8 component first, at an infusion rate of approximately 0.5 mL/min, ensuring that all syringes or vials of the CD8 component are administered consecutively without any delay between each syringe or vial, unless the patient develops IRR.⁴ After completion of the CD8 component infusion, flush the tubing with enough NS to clear the tubing and IV catheter length.

Administer the CD4 component second, immediately after the complete administration of the CD8 component and following the same steps as described for the CD8 component with an infusion rate of approximately 0.5 mL/minute. Upon completion of the CD4 component, flush the tubing with NS, ensuring enough volume is used to clear the tubing length and the length of the IV catheter.

The Recommended Dose

The expected dose range for follicular lymphoma is from 90 to 110 x10⁶ CAR-positive viable T cells. Since liso-cel is a personalized medication, the actual dose will vary for each patient.^3,4

How to Manage Associated Adverse Events (AEs)

Hypersensitivity reactions: Allergic reactions may occur with treatment infusion. Reactions may include anaphylaxis due to dimethyl sulfoxide and should be managed per clinical practice guidelines.

Cytokine release syndrome (CRS): CRS occurred in 56% of patients, including grade 3 or worse CRS in 3.4% of patients with a non-Hodgkin lymphoma in clinical studies receiving liso-cel. The most common manifestations of CRS, occurring in at least 10% of patients, were fever, hypotension, tachycardia, chills, hypoxia, and headache. At the first sign of CRS, institute treatment with supportive care or tocilizumab with or without corticosteroids as indicated.

Immune effector cell–associated neurotoxicity syndrome (ICANS): Thirty-two percent of patients in clinical studies developed neurologic toxicities, including grade 3 or worse cases in 10% of patients. The most common neurologic toxicities, occurring in at least 5% of patients, included encephalopathy, tremor, aphasia, headache, and delirium. Of patients developing neurotoxicity, 83% also developed CRS. Management includes supportive care and/or corticosteroid as needed and clinically indicated.

Serious infections: Infections occurred in 33% of patients, with grade 3 or higher infections occurring in 12% of patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, with bacterial and viral infections observed in posttreatment observation. Monitor all patients for signs and symptoms of infection pre- and posttreatment and avoid administration in patients with clinically significant or active systemic infections. Consideration for prophylactic antimicrobials and anti-infective agents should be considered post treatment if clinically indicated.

Prolonged cytopenias: Grade 3 or higher cytopenias continued at day 29 following infusion in 35% of patients, including thrombocytopenia in 25%, neutropenia in 22%, and anemia in 6% of patients. Monitor complete blood counts before and after treatment, paying attention to potential severe AEs⁵ and consider intervention according to clinical guidelines.

Hypogammaglobulinemia: Observed in 30% of patients after treatment,³ hypogammaglobulinemia increases the risk of infections in patients.³ As part of ongoing follow-up, monitor immunoglobulin levels. Management may include infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.

Secondary malignancies: Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion and may include fatal outcomes. Monitor lifelong for secondary malignancies, and manage as clinically indicated if a malignancy is identified.

Immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS): The development of features of IEC-HS is independent of CRS and ICANS but attributed to therapy, with symptoms including new onset or worsening cytopenia, hyperferritinemia with hypofibrinogenemia, and transaminitis.⁵ It can be fatal or have a severe life-threatening impact and was observed in less than 1% of patients receiving liso-cel with relapsed or refractory non-Hodgkin lymphoma.^3,4 Treatment should be administered in accordance with institutional and clinical practice guidelines.

What to Inform Patients Before Starting Treatment

Inform patients about all symptoms of IRR prior to starting therapy and to report any symptoms to their clinical team during and after treatment infusion. Due to the risk of CRS and ICANS, patients must comply with daily monitoring for at least 7 days after treatment, with less frequent monitoring for at least 4 weeks after treatment. Patients are required to stay within 2 hours of the treatment center to ensure prompt treatment of toxicities if they develop, and must seek immediate medical attention if they develop any signs or symptoms.^3,4

Advice for Nurses Who Administer This Agent

Nursing considerations include confirming tocilizumab availability before infusion; observing patients for signs of AEs, including CRS and neurotoxicity; and reinforcing patient education on symptom reporting.^3,4,6 Nurses play a key role in patient safety and effective management of CAR T-cell therapy.

References

1. FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. FDA. May 15, 2024. Accessed April 4, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma.
2. Morschhauser F, Dahiya S, Palomba ML, et al. TRANSCEND FL: phase 2 study primary analysis of lisocabtagene maraleucel as second-line therapy in patients with high-risk relapsed or refractory follicular lymphoma. Blood. 2023;142(suppl 1):602. doi:10.1182/blood-2023-179474
3. Breyanzi. Prescribing information. Bristol Myers Squibb; 2025. Accessed December 19, 2025. https://packageinserts.bms.com/pi/pi_breyanzi.pdf
4. Breyanzi. Dosing and administration. Bristol Myers Squibb; 2025. Accessed December 23, 2025. https://www.breyanzihcp.com/assets/commercial/us/breyanzihcp/en/pdfs/Breyanzi_Dosing_and_Administration_Quick_Reference_Guide.pdf
5. Ebinama U, Prakash R, Strati P, et al. Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS): a review of pharmacovigilance. Blood. 2023;142(suppl 1):5132. doi:10.1182/blood-2023-185190
6. 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