The Food and Drug Administration has approved axicabtagene ciloleucel (Yescarta) for adults with large B-cell lymphoma, a type of non-Hodgkin lymphoma. Axicabtagene ciloleucel is a second-line drug for patients who are resistant to, or who relapse within 12 months of, first-line chemoimmunotherapy. It is not indicated for the treatment of primary central nervous system lymphoma.
Axicabtagene ciloleucel is a CD19-directed, genetically modified, autologous T-cell immunotherapy. Using leukapheresis, the patient's white blood cells are collected and concentrated. They are then formulated into a drug specific to the individual patient for IV infusion. The concentrated white blood cells that are reintroduced into the patient recognize and eliminate CD19-expressing target cells.
Axicabtagene ciloleucel's labeling carries two boxed warnings: one for cytokine release syndrome (an acute, systemic inflammatory syndrome caused by a large, rapid release of cytokines into the blood from immune cells), which can be life-threatening or fatal; and another for neurologic toxicities, including fatal or life-threatening reactions, which can be concurrent with cytokine release syndrome or occur after its resolution. Because of these boxed warnings, axicabtagene ciloleucel is only available through a Risk Evaluation and Mitigation Strategy (REMS) program. Other warnings include hypersensitivity reactions, serious infections, prolonged cytopenias, hypogammaglobulinemia, and secondary malignancies.
The most common nonlaboratory adverse reactions in addition to cytokine release syndrome are fever, hypotension, encephalopathy, fatigue, tachycardia, headache, nausea, febrile neutropenia, diarrhea, musculoskeletal pain, infections, chills, and decreased appetite. Dizziness and lightheadedness, fatigue, insomnia, muscle weakness, memory changes, or confusion may also occur, but less frequently. The most common grade 3 or 4 laboratory abnormalities are leukopenia, lymphopenia, neutropenia, anemia, thrombocytopenia, and hypophosphatemia.
Approval of axicabtagene ciloleucel was based on a randomized, open-label multicenter trial of 359 patients who had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation (HSCT). The patients were randomized 1:1 to receive either a single infusion of axicabtagene ciloleucel following fludarabine and cyclophosphamide lymphodepleting chemotherapy or second-line standard therapy consisting of two or three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in patients who attained complete or partial remission. The primary efficacy measure was event-free survival, which was significantly longer for those who received axicabtagene ciloleucel than for those who did not. The estimated 18-month event-free survival rate was 41.5% in the axicabtagene ciloleucel arm and 17% in the standard therapy arm; the estimated median event-free survival was 8.3 months and two months, respectively.
Nurses administering axicabtagene ciloleucel should confirm the patient's identity and match it to the drug, as this is an autologous infusion. Patients should be premedicated with acetaminophen and an H1 antihistamine to minimize the risk of hypersensitivity reactions. To minimize cytokine release syndrome, axicabtagene ciloleucel should not be administered to patients with active infection or inflammatory disorders. Severe or life-threatening cytokine release syndrome should be treated with tocilizumab or tocilizumab and corticosteroids. Tocilizumab should be on hand prior to starting axicabtagene ciloleucel.
To minimize the risk of adverse effects, nurses should monitor for hypersensitivity reactions during infusion, signs and symptoms of infection, prolonged cytopenias (this can last for several weeks after infusion), complete blood counts, hypogammaglobulinemia, and secondary malignancies. If a secondary malignancy occurs, the manufacturer, Kite Pharma, should be contacted at 1-844-454-KITE (5483). Adverse effects can be reported to the FDA MedWatch program at http://www.fda.gov/medwatch/report.htm.
Nurses should tell patients not to drive, operate heavy equipment, or engage in dangerous tasks for eight weeks after infusion, as changes in alertness and mental focus or dizziness can occur with treatment.
For complete prescribing information for axicabtagene ciloleucel, go to http://www.fda.gov/media/108377/download.