FDA Investigating ‘Serious Risk’ of Malignancy After CAR T Therapy

By Steve Blanchard - December 05, 2023

Recent concerns have prompted an investigation by the Food and Drug Administration into what is called a “serious risk” of T-cell malignancies in patients treated with autologous chimeric antigen receptor T-cell therapies (CAR T). Reports include patients with CAR-positive lymphomas.

CAR T has revolutionized the treatment of blood cancers. The single infusion of genetically modified immune cells has led to durable remissions for patients with few to no other treatment options.

The FDA has received multiple reports of T-cell malignancies with some resulting in hospitalization and death.

According to Dr. Frederick Locke, chair of the Blood and Marrow Transplant and Cellular Immunotherapy Department and co-leader of the Immuno-Oncology Program at Moffitt Cancer Center, there is still value to CAR T therapy for patients without other viable treatment options.

“That said, it is not out of the realm of possibility that one or two out of 10,000 patients could develop T-cell lymphoma,” Locke said.

portrait of blockquote author

"It is not out of the realm of possibility that one or two out of 10,000 patients could develop T-cell lymphoma."

- Dr. Frederick Locke, Blood and Marrow Transplant and Cellular Immunotherapy Department

“In addition, several patients previously developed CAR-positive T-cell lymphoma after receiving an investigational CAR that utilized transposon technology, which is not used with FDA-approved CAR T cells,” he added. “Finally, we know that cancer immunotherapy such as checkpoint blockade for solid tumors, which does not rely on gene therapy, can very rarely result in T-cell lymphomas.”

The investigation includes all currently approved BCMA- and CD19-targeted CAR T-cell products:

  • Axicabtagene ciloleucel (Yescarta)
  • Brexucabtagene autoleucel (Tecartus)
  • Ciltacabtagene autoleucel (Carvykti)
  • Lisocabtagene maraleucel (Breyanzi)
  • Tisagenlecleucel (Kymriah)

“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 hospitalizations and death, and is evaluating the need for regulatory action,” FDA officials said in a statement. “As with all gene therapy products with integrating vectors (lentiviral or retroviral vectors), the potential risk of developing secondary malignancies is labeled as a class warning in the U.S. prescribing information for approved BCMA-directed and CD19-directed genetically modified autologous T-cell immunotherapies.”

According to the FDA, the agency has received 19 reports of CAR-associated T-cell malignancies, five from clinical trials and 14 from the FDA’s adverse event reporting system. The agency is investigating “the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death.”

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