On October 18 the Food and Drug Administration (FDA) approved a new cell-based cancer immunotherapy for patients with advanced lymphoma. Yescarta, produced by Kite Pharma, a Gilead company, is the second chimeric antigen receptor T cell (CAR-T) gene therapy to win FDA approval and the first to be approved for adults of any age.

Yescarta, also known by the tongue-twisting name axicabtagene ciloleucel, is indicated for adults with certain types of large B-cell lymphoma who have tried at least two other kinds of treatment and either did not respond or relapsed. The approval does not include primary central nervous system lymphoma.

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma, striking around 24,000 people in the United States each year, according to the FDA. Gilead Sciences estimates that approximately 7,500 people with refractory disease will be eligible for CAR-T therapy.

“Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases,” FDA commissioner Scott Gottlieb, MD, said in a press release. “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.”

CAR-T therapy involves removing a sample of a patient’s white blood cells, genetically reprogramming them to kill cancer cells, multiplying them in the laboratory and infusing them back into the body. The procedure uses gene therapy to modify a patient’s own T cells, the main soldiers of the immune system, making them better able to track down and attack cancer cells.

Yescarta was originally developed by Steven Rosenberg, MD, and colleagues at the National Cancer Institute, one of three teams that pioneered CAR-T, along with Carl June, MD, and colleagues at the University of Pennsylvania and Michel Sadelain, MD, and colleagues at Memorial Sloan-Kettering Cancer Center. Gilead acquired Kite this year to gain access to the CAR-T technology and a foothold in oncology.

In the multicenter ZUMA-1 trial, which enrolled more than 100 adults with refractory or relapsed large B-cell lymphoma, 51 percent of patients treated with a single infusion of Yescarta achieved complete remission, or no detectable remaining cancer. The overall response rate (complete and partial remission combined) was 72 percent, according to Gilead. The median duration of response could not be determined because most patients were still responding.

“With CAR-T therapy, we are reengineering a patient’s own immune system to detect and kill cancer cells, and the results have been impressive,” ZUMA-1 investigator Frederick Locke, MD, of Moffitt Cancer Center in Tampa said in a Gilead press release. “Many of the patients that received CAR-T therapy had already relapsed several times with traditional treatments such as chemotherapy or hematopoietic stem cell transplant. Now, thanks to this new therapy many patients are in remission for months.”

In July, the FDA’s Oncologic Drugs Advisory Committee heard testimony from researchers, industry representatives and patients and their parents about the effectiveness, safety and manufacturing process for the Novartis CAR-T Kymriah (tisagenlecleucel), which was approved in late August for children and young adults with advanced leukemia. The agency did not require the same kind of extensive review for Yescarta, as many of the safety concerns and manufacturing issues are similar across CAR-T therapies.

Yescarta can cause potentially life-threatening side effects including cytokine release syndrome (CRS), or a “cytokine storm,” with symptoms ranging from fever and flu-like illness to neurological problems and organ failure. Unleashing genetically modified T cells not only kills cancer cells but can also trigger an excessive immune response that harms healthy tissue. The new therapy can also cause low white blood cell counts, raising the risk of infections.

More than 90 percent of ZUMA-1 participants developed CRS, usually within a couple of days after treatment, according to Gilead. The proportion with severe symptoms was much lower (13 percent), but four patients with CRS died. A similar proportion (87 percent) developed neurological toxicities including encephalopathy, headache and tremors, which were severe in 31 percent.

The FDA will require hospitals administering Yescarta to be specially certified and trained to manage cytokine release syndrome and nervous system side effects, and they must have the immunosuppressant drug Actemra (tocilizumab) immediately available.

Yescarta will be produced at Kite’s commercial manufacturing facility in El Segundo, California, using patients’ T cells that are collected, frozen and shipped from 16 cancer centers across the country, with an eventual target of up to 90 centers. In the ZUMA-1 trial, Kite achieved a 99 percent manufacturing success rate with a median turnaround time of 17 days, Gilead said.

Gilead set the price for Yescarta at $373,000, below the $475,000 price tag for Kymriah. Gilead has not said whether it will adopt Novartis’s policy of only charging if patients respond to treatment.

CAR-T therapy is a labor- and technology-intensive treatment that is customized for each individual, and its high price raises questions about how patients will be able to access this kind of effective but expensive personalized therapy. However, its cost compares favorably with that of bone marrow transplants, which can run upwards of $500,000.

Yescarta is also being studied for other blood cancers. Besides Kite/Gilead and Novartis, other companies developing CAR-T therapies include Bluebird Bio, Cellectis, Juno Therapeutics and Mustang Bio. While this type of therapy so far is only approved for a small subset of patients with specific cancer types and prior treatment histories, it will likely see broader use in the future, especially if scaled-up production can reduce its cost.

Click here to read an FDA press release about Yescarta approval.

Click here to read a Gilead press release about Yescarta approval.

Click here for prescribing information and safety warnings for Yescarta.