The Food and Drug Administration has approved an additional indication for lisocabtagene maraleucel (Breyanzi) to treat adults with large B-cell lymphoma who have 1) lost responsiveness to first-line chemoimmunotherapy and relapsed within 12 months or 2) lost responsiveness to first-line chemoimmunotherapy or relapsed after first-line chemoimmunotherapy and aren't eligible for hematopoietic stem cell transplantation because of comorbidities or age. Lisocabtagene maraleucel was first approved in 2021 to treat large B-cell lymphoma after two or more lines of systemic therapy were no longer effective. Lisocabtagene maraleucel is not indicated for the treatment of patients with primary central nervous system lymphoma.

Lisocabtagene maraleucel is a CD19-directed, genetically modified, autologous T-cell immunotherapy. It is prepared from a patient's T cells via leukapheresis. The T cells are genetically modified to include a new gene that aids in targeting and killing the lymphoma cells. Once the cells are modified, they are infused back into the patient.

Lisocabtagene maraleucel's efficacy was evaluated in the randomized, open-label, multicenter TRANSFORM trial in 184 adult patients with large B-cell lymphoma who either had relapsed or were refractory after first-line therapy. Patients had not yet received treatment and were potential candidates for autologous hematopoietic stem cell transplantation. Patients were randomized 1:1 to receive either a single infusion of lisocabtagene maraleucel following fludarabine and cyclophosphamide lymphodepleting chemotherapy or second-line standard therapy consisting of three cycles of chemoimmunotherapy followed by high-dose therapy and autologous hematopoietic stem cell transplantation in patients who attained complete or partial response. Event-free survival was significantly longer in the lisocabtagene maraleucel arm. The estimated one-year event-free survival was 45% in the lisocabtagene maraleucel arm and 24% in the standard therapy arm.

Efficacy was also evaluated in the single-arm, open-label, multicenter PILOT trial of 74 transplant-ineligible patients with relapsed or refractory large B-cell lymphoma after one line of chemoimmunotherapy. Complete response was achieved in 54% of those who received lisocabtagene maraleucel.

Lisocabtagene maraleucel continues to be prescribed under the Risk Evaluation and Mitigation Strategy because of the risk of fatal or potentially fatal cytokine release syndrome and neurologic toxicities. These are listed as boxed warnings in the product's labeling. The most common manifestations of cytokine release syndrome are fever (94%), hypotension (42%), tachycardia (28%), chills (23%), hypoxia (16%), and headache (12%). Other serious presentations of cytokine release syndrome are cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. The most common neurologic toxicities are encephalopathy (20%), tremor (13%), aphasia (8%), headache (6%), dizziness (6%), and delirium (5%).

A lymphodepleting chemotherapy regimen should be infused two to seven days before infusing lisocabtagene maraleucel. It is important to confirm the patient's identity prior to infusing lisocabtagene maraleucel, as it is an autologous product and can only be given to the patient from whom the cells were collected during leukapheresis. The product must be thawed prior to infusion. Nurses should carefully read the package insert for specific directions on thawing, preparing, and administering the separate infusions of CD8 and CD4 components.

To minimize the risk of infusion reactions, nurses should premedicate the patient with oral acetaminophen and either oral or IV diphenhydramine. Systemic prophylactic corticosteroids may interfere with the activity of lisocabtagene maraleucel and should be avoided. Nurses should monitor all patients receiving lisocabtagene maraleucel for at least seven days after infusion for signs or symptoms of cytokine release syndrome or neurologic toxicities. Tocilizumab should be available prior to administration of lisocabtagene maraleucel and administered if cytokine release syndrome occurs. IV corticosteroid treatment for cytokine release syndrome is another option. Emergency equipment (such as a crash cart) should be accessible in case of adverse effects from lisocabtagene maraleucel. The nurse should keep the package insert until the risk of adverse effects has been ruled out, as it describes treatments for various grades of cytokine release syndrome and neurotoxicities.

For complete prescribing information for lisocabtagene maraleucel, go to http://www.fda.gov/media/145711/download.