1. Aschenbrenner, Diane S. MS, RN


* Lisocabtagene maraleucel (Breyanzi), a personalized cell-based gene therapy, has been approved to treat adults with various relapsed or refractory large B-cell lymphomas.



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Lisocabtagene maraleucel (Breyanzi), a personalized cell-based gene therapy, has been approved by the Food and Drug Administration (FDA) to treat diffuse large B-cell lymphoma (the most common type of non-Hodgkin lymphoma in adults), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B in adults who have not responded to, or have relapsed following, at least two other types of systemic treatment for lymphoma. Lisocabtagene maraleucel is administered two to seven days after completing a lymphodepleting chemotherapy regimen of fludarabine and cyclophosphamide.


Lisocabtagene maraleucel is a CD19-directed, genetically modified, autologous T-cell immunotherapy. The patient's T cells are obtained using a standard leukapheresis procedure. The CD8-positive and CD4-positive T cells are separated and genetically modified to selectively recognize and kill the patient's lymphoma cells. Once the T cells are modified, the CD4 and CD8 components are kept in separate patient-specific vials and shipped back as frozen suspensions. The genetically modified T cells are then thawed and infused back into the patient.


The efficacy of lisocabtagene maraleucel was evaluated in an open-label, multicenter, single-arm trial in adult patients with relapsed or refractory large B-cell non-Hodgkin lymphoma after at least two lines of therapy. The remission rate after treatment was 54%.


Lisocabtagene maraleucel carries a boxed warning related to cytokine release syndrome and neurologic toxicities. Cytokine release syndrome is an acute, overactive immune system response in which a large and rapid release of cytokines occurs. This strong immune response can bring about fatal or life-threatening reactions. The most common signs and symptoms of cytokine release syndrome include fever, chills, hypotension, tachycardia, hypoxia, and fatigue. Other serious adverse effects associated with cytokine release syndrome are cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome.


The most common neurologic toxicities related to lisocabtagene maraleucel treatment include encephalopathy, tremor, aphasia, delirium, headache, ataxia, and dizziness. Other serious adverse effects are cerebral edema and seizures. Because of the risk of serious and potentially life-threatening cytokine release syndrome and neurotoxicities, lisocabtagene maraleucel is only available at health care facilities certified to administer lisocabtagene maraleucel through a restricted FDA program known as Risk Evaluation and Mitigation Strategy (REMS).


The product's labeling also warns of the risk of hypersensitivity reactions, serious infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, and altered ability to drive or operate machinery. The most common adverse effects of treatment are fatigue, cytokine release syndrome, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema.


Nurses caring for patients prescribed lisocabtagene maraleucel should confirm that it is available prior to starting the lymphodepleting chemotherapy, which should be administered first, daily, for three days. Lisocabtagene maraleucel should be infused two to seven days after the chemotherapy. The infusion should be delayed if the patient has unresolved serious adverse effects from the chemotherapy, active uncontrolled infection, or active graft-versus-host disease.


Patients should be premedicated with oral acetaminophen and oral or intravenous diphenhydramine, or another H1-antihistamine, 30 to 60 minutes prior to infusing lisocabtagene maraleucel. Prophylactic systemic corticosteroids should not be used, as they may interfere with the activity of lisocabtagene maraleucel.


Nurses should ensure that two doses of tocilizumab are available prior to infusion of lisocabtagene maraleucel. Tocilizumab is an interleukin-6 receptor blocker monoclonal antibody with antiinflammatory properties; it is approved for the treatment of severe or life-threatening T-cell-induced cytokine release syndrome. Emergency equipment should also be available during lisocabtagene maraleucel infusion.


After the vials of lisocabtagene maraleucel have been defrosted and the drug has been drawn into syringes, it should be administered within two hours. Lisocabtagene maraleucel is individually made for each patient and must be used only by that patient. Proper patient identification is crucial prior to administration. Infusion tubing should be flushed with normal saline prior to and after each CD8 and CD4 component administration. The CD8 component should be infused first, then the CD4 component.


Adverse effects generally appear within the first two weeks after lisocabtagene maraleucel treatment but can occur later. Patients need monitoring daily and for at least four weeks after infusion to assess for cytokine release syndrome, neurologic toxicities, and other adverse effects. Nurses should teach patients to seek emergency help immediately if the following potential life-threatening adverse effects occur: difficulty breathing, fever (100.4[degrees]F/38[degrees]C or higher), chills or shaking chills, confusion, severe nausea, vomiting, diarrhea, fast or irregular heartbeat, dizziness/lightheadedness, or severe fatigue or weakness.


Patients should not drive or engage in hazardous activities for eight weeks after receiving lisocabtagene maraleucel because of the risk of fatigue. Patients should contact Bristol Myers Squibb, the drug's manufacturer, at (888) 805-4555 if they are diagnosed with a secondary malignancy.


For complete prescribing information for lisocabtagene maraleucel, go to