Medication Monitor

Generic Name (Trade Name—Company)
August 30, 2017


FDA approval of tisagenlecleucel for ALL brings first gene therapy to the United States

FDA approved tisagenlecleucel for pediatric and young adult patients (up to age 25 y) with with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. It is the first gene therapy available in the United States, ushering in a new approach to treatment of cancer and other serious and life-threatening diseases, according to an FDA news release.

Tisagenlecleucel is a genetically modified autologous T-cell immunotherapy. Each dose is a customized treatment created using an individual patient’s own T-cells, which are collected and sent to a manufacturing center, where they are genetically modified to include a new gene that contains a chimeric antigen receptor (CAR) that directs the T-cells to target and kill leukemia cells that have a CD19 antigen on the surface. Once the cells are modified, they are infused back into the patient to kill the cancer cells.

The agent's safety and efficacy were demonstrated in one multicenter clinical trial of 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL. The overall remission rate within 3 months of treatment was 83%.

Treatment with tisagenlecleucel may cause severe adverse 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 flulike symptoms, and for neurological events. Both CRS and neurological events can be life-threatening.

Other adverse effects include serious infections, low blood pressure, acute kidney injury, fever, and decreased oxygen. Most symptoms appear within 1 to 22 days following infusion.

Because the CD19 antigen is also present on normal B cells, and tisagenlecleucel will also destroy those normal B cells that produce antibodies, there may be an increased risk of infections for a prolonged period of time.

Because of the risk of CRS and neurological events, tisagenlecleucel is being approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU).

FDA is requiring that hospitals and their associated clinics that dispense tisagenlecleucel be specially certified. As part of that certification, staff involved in the prescribing, dispensing, or administering of tisagenlecleucel are required to be trained to recognize and manage CRS and neurological events.

In addition, the certified health care settings are required to have protocols in place to ensure that tisagenlecleucel is given only to patients after verifying that tocilizumab is available for immediate administration. The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion, as well as the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment.

To further evaluate the long-term safety, Novartis is also required to conduct a postmarketing observational study involving patients treated with tisagenlecleucel.