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The FDA recently announced that it had launched an investigation of a cancer treatment pioneered by Penn Medicine.

Credit: Abhiram Juvvadi

The United States Food and Drug Administration announced that it was opening an investigation into CAR-T therapy, a cancer treatment that was pioneered at Penn.

The investigation centers on the possibility that the therapy may cause cancer in rare cases, following reports of T cell malignancy in those who received the treatment. Penn Medicine said in a statement to The Daily Pennsylvanian that it plans to continue offering the treatment to patients.

Chimeric antigen receptor T cell immunotherapy modifies a patient’s T cells to target and kill their own cancer cells. More than 20,000 patients worldwide — including hundreds of Penn Medicine patients — have been treated with the technique since 2010, according to David Porter, the director of Cell Therapy and Transplantation at Penn Medicine’s Abramson Cancer Center.

"Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action," the FDA said in its announcement on Nov. 28.

Porter told the DP that he was surprised by the investigation and was not previously aware of the cases of "rare, secondary lymphomas."

"Currently, it’s unclear whether genetically modified T cells caused the secondary cancers or if other risk factors may be at play,” Porter wrote. “Health circumstances, such as immunosuppression status, previous chemotherapy, or certain preexisting stem cell conditions, could increase the chances of developing a secondary cancer."

Porter also told the DP that Penn Medicine — as a leader in CAR-T therapy’s development — has longstanding protocols to monitor patients after receiving the therapy, including follow-up for 15 years, and has not seen any cases of secondary lymphomas.

"Nevertheless, we are aware that this is a theoretical possibility and indeed is one of the reasons we participate in a meticulous long-term follow-up program," Porter wrote.

Porter noted that Penn Medicine feels as though the benefits of CAR-T therapy continue to outweigh potential risks. He wrote that Penn Medicine will continue to work with patients to ensure that they receive the best possible treatment plans for their specific cancer types and goals, and that in the vast majority of cases, CAR-T therapy is only used after other therapies fail to stop cancers from progressing.

Penn researchers, including cancer scientist Carl June, first used CAR-T cell therapy to treat adult leukemia patients in 2010. A 2012 Penn Medicine press release stated that June’s findings were the first demonstration of the use of gene transfer therapy to create "serial killer" T cells targeting cancerous tumors.

In 2012, Penn partnered with Swiss pharmaceutical company Novartis to continue research into CAR-T cell therapy. The partnership involved the construction of new cancer research facilities at the University to increase its patient treatment capacity. In 2016, the University — along with five peer institutions — received a $250 million grant to found the Parker Institute for Cancer Immunotherapy and develop new cancer treatment techniques, with June named one of the Institute's new directors.

The first CAR-T therapy — made by Novartis — was approved by the FDA in 2017 for treatment of pediatric and young adult patients with B cell acute lymphoblastic leukemia. 

"I have to keep pinching myself to see that this happened," June said to The New York Times in 2017. "It was so improbable that this would ever be a commercially approved therapy, and now it’s the first gene therapy approved in the United States. It’s so different from all the pharmaceutical models. I think the cancer world is forever changed."

Multiple other CAR-T therapies have been approved since 2017. The FDA press release from Nov. 28 stated that the agency is investigating six CAR-T therapies for lymphoma and leukemia, including therapies by Bristol-Myers Squibb, Johnson & Johnson, and Gilead.

In statements to the DP, Bristol-Myers Squibb, Novartis, and Johnson & Johnson confirmed their awareness of and cooperation with the FDA investigation. The three companies stated that they remain confident in the favorability of the benefit-risk profiles of their respective treatments.

Gilead did not respond to a request for comment.

"As part of post-CAR-T therapy safety and surveillance, regulatory agencies require testing of secondary primary malignancies in patients receiving cell and gene therapies both in clinical research and in the commercial setting," Johnson & Johnson Global Oncology and R&D Communication Leader Brian Kenney wrote to the DP. "We have shared our data with the FDA and are working with the agency as they assess this newly identified class-effect safety signal."