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While this article is not specific about chronic lymphocytic leukemia, it is still huge news for all of us with CLL
From Oct. 18, on the FDA’s website:
“The U.S. Food and Drug Administration today approved Yescarta (axicabtagene ciloleucel), 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. 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).”
“Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases. In just several decades, gene therapy has gone from being a promising concept to a practical solution to deadly and largely untreatable forms of cancer,” said FDA Commissioner Scott Gottlieb, M.D.
The treatment, called Yescarta is made by Gilead Sciences who purchased it from Kite.
Each dose is a customized therapy created using the patient’s own immune cells to help fight the cancer. The patient’s T-cells, a type of lymphocyte, are collected and genetically modified by using a harmless virus to introduce a new gene that targets CD19 with the goal to kill the lymphoma cells. Once the cells are modified, they are infused back into the patient.
A chimera refers to Greek mythology, an incongruous blend of more than one animal. In this case our chimera is a virus and a human T-cell.
Here is a cool video from Dana Farber on the process: https://youtu.be/OadAW99s4Ik
Yescarta was approved after a six-month trial of 101 patients with an aggressive form of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), a cancer that affects immune cells, a distant cousin to CLL, and the most common type of NHL in adults.
Yescarta cured 36% of patients completely, and in more than 8 out of 10 patients, their tumors shrunk to less than half their original size in this difficult to treat population.
In August of this year, the FDA had approved the first “gene therapy’, CAR-T for a form of childhood leukemia. Kymriah is made by Novartis and has much higher success rates in clinical trials, curing 83% of childhood patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)
CAR-T therapies are a real possibility now for those patients who would otherwise be out of options, but they come with heavy risks and strict indications.
Yescarta carries a boxed warning (the most emphatic possible warning on the drug’s package insert) for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells. It causes high fever, low blood pressure, and flu-like symptoms, and neurologic toxicities. Both CRS and neurologic toxicities can be fatal. Other side effects include serious infections, low blood cell counts and a weakened immune system. Two patients in the trial died of severe brain damage associated with the drug.
Similar side effects have been seen with the first FDA-approved CAR-T therapy and in early trials for Juno and other CAR-T being developed to treat for CLL.
Because these drugs are so expensive (Yescarta costs $373,000. Kymriah $475,000), it is most unlikely that insurance will pay for them off-label. They will only be covered for their specific indications, in other words, for what they were tested for, though there is good reason to believe they would work on CLL and other blood cancers that also carry a CD19 antigen.
For now the only option for us CLL patients are clinical trials. Here are two that are recruiting right now.
More are coming all the time, but because these are bespoke drugs, trials are small and openings few.
Here is a link to a nice article told from the patient’s perspective on CAR-T: https://www.statnews.com/2017/10/27/car-t-kite-cell-journey/
The CLL Society will be producing more educational material on this important new therapy. Watch for “CART-Y” to debut soon.
Brian Koffman, MD 10/31/17