October 19, 2017 – The American  Food & Drug Administration (FDA) just approved Axicabtagene Ciloleucel (Yescarta), a cell-based gene therapy, to treat adult patients with certain types of large B-cell lymphoma who have not responded to or who have relapsed after at least two other kinds of treatment. Axicabtagene Ciloleucel (Yescarta), a chimeric antigen receptor (CAR) T cell therapy, is the second gene therapy approved by the FDA and the first for certain types of non-Hodgkin lymphoma (NHL).

Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL in adults. NHLs are cancers that begin in certain cells of the immune system and can be either fast-growing (aggressive) or slow-growing. Approximately 72,000 new cases of NHL are diagnosed in the U.S. each year, and DLBCL represents approximately one in three newly diagnosed cases. Axicabtagene Ciloleucel (Yescarta) is approved for use in adult patients with large B-cell lymphoma after at least two other kinds of treatment failed, including DLBCL, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Axicabtagene Ciloleucel (Yescarta) is not indicated for the treatment of patients with primary central nervous system lymphoma.

Each dose of Axicabtagene Ciloleucel (Yescarta) is a customized treatment created using a patient’s own immune system to help fight the lymphoma. The patient’s T-cells, a type of white blood cell, are collected and genetically modified to include a new gene that targets and kills the lymphoma cells. Once the cells are modified, they are infused back into the patient.

The efficacy  of Axicabtagene Ciloleucel (Yescarta) was established in a multicenter clinical trial of more than 100 adult patients with refractory or relapsed large B-cell lymphoma. The complete remission rate after treatment with Yescarta was 51 percent.

Be aware however, that the treatment with Axicabtagene Ciloleucel (Yescarta) has the potential to cause severe side effects. It carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, and for neurologic toxicities. Both CRS and neurologic toxicities can be fatal or life-threatening.

Thus, CRS, including fatal or life-threatening reactions, occurred following treatment with Axicabtagene Ciloleucel (Yescarta). In one tudy, CRS occurred in 94% (101/108) of patients receiving Axicabtagene Ciloleucel (Yescarta), including ≥ Grade 3 (Lee grading system) CRS in 13% (14/108) of patients. Among patients who died after receiving Yescarta, four had ongoing CRS events at the time of death.

The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%) and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures occurred with Axicabtagene Ciloleucel (Yescarta). Fatal and serious cases of cerebral edema have occurred in patients treated with Axicabtagene Ciloleucel (Yescarta).

Other side effects include serious infections, low blood cell counts and a weakened immune system. Side effects from treatment with Axicabtagene Ciloleucel (Yescarta) usually appear within the first one to two weeks, but some side effects may occur later.

Because of the risk of CRS and neurologic toxicities, Axicabtagene Ciloleucel (Yescarta) is being approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU). The FDA is requiring that hospitals and their associated clinics that dispense Axicabtagene Ciloleucel (Yescarta) be specially certified. As part of that certification, staff involved in the prescribing, dispensing or administering of Axicabtagene Ciloleucel (Yescarta) are required to be trained to recognize and manage CRS and nervous system toxicities. Also, patients must be informed of the potential serious side effects and of the importance of promptly returning to the treatment site if side effects develop. To further evaluate the long-term safety, the FDA is also requiring the manufacturer to conduct a post-marketing observational study involving patients treated with Axicabtagene Ciloleucel (Yescarta).

The FDA granted Axicabtagene Ciloleucel (Yescarta) Priority Review and Breakthrough Therapy as well as Orphan Drug designation; the latter provides incentives to assist and encourage the development of drugs for rare diseases.