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Kymriah for B-cell precursor acute lymphoblastic leukemia: important safety information

Kymriah ( Tisagenlecleucel ), a cell-based gene therapy, is approved in the United States for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia ( ALL ) that is refractory or in second or later relapse.

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

Kymriah may cause side effects that are fatal or life-threatening, such as cytokine release syndrome ( CRS ) or neurological toxicities.

Patients with cytokine release syndrome may experience symptoms including high fever, difficulty breathing, chills/shaking chills, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure or dizziness/lightheadedness.
Patients may be admitted to the hospital for cytokine release syndrome and treated with other medications.

Patients with neurological toxicities may experience symptoms such as altered or decreased consciousness, headaches, delirium, confusion, agitation, anxiety, seizures, difficulty speaking and understanding, or loss of balance.

Because of the risk of cytokine release syndrome and neurological toxicities, Kymriah is only available through a restricted program under a Risk Evaluation and Mitigation Strategy ( REMS ) called Kymriah REMS.

Serious allergic reactions, including anaphylaxis, may occur after Kymriah infusion.
Kymriah can increase the risk of life-threatening infections that may lead to death.
Patients should be advised to tell their health care provider right away if they develop fever, chills, or any signs or symptoms of an infection.

Patients may experience prolonged low blood cell counts ( cytopenia ), where one or more types of blood cells ( red blood cells, white blood cells, or platelets ) are decreased.

Patients may experience hypogammaglobulinemia, a condition in which the level of immunoglobulins ( antibodies ) in the blood is low and the risk of infection is increased.
It is expected that patients may develop hypogammaglobulinemia with Kymriah, and may need to receive immunoglobulin replacement for an indefinite amount of time following treatment with Kymriah.
Patients should tell inform health care provider about their treatment with Kymriah before receiving a live virus vaccine.

After treatment with Kymriah, patients will be monitored life-long by their health care provider, as they may develop secondary cancers or recurrence of their leukemia.

Patients should not drive, operate heavy machinery, or do other dangerous activities for 8 weeks after receiving Kymriah because the treatment can cause temporary memory and coordination problems, including sleepiness, confusion, weakness, dizziness and seizures.

Some of the most common side effects of Kymriah included: difficulty breathing, fever ( 100.4°F/38°C or higher ), chills/shaking chills, confusion, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, and dizziness / lightheadedness.

Prior to a female patient starting treatment with Kymriah, health care provider may do a pregnancy test. There is no information available for Kymriah use in pregnant or breast-feeding women. Therefore, Kymriah is not recommended for women who are pregnant or breast feeding. ( Xagena )

Source: Novartis, 2017