Concerns Over Secondary Cancer Risk Prompt FDA to Require Warnings on CAR T-Cell Therapies


The FDA made the decision to require boxed warnings on CAR T-cell therapies based on reports of T-cell malignancies in patients administered BCMA- or CD19-directed autologous CAR T-cell immunotherapies.

Image credit: LASZLO |

Image credit: LASZLO |

On January 19, 2024, the FDA issued multiple notifications to drugmakers requiring boxed warnings to be added to all chimeric antigen receptor (CAR) T-cell therapy products, citing additional cancer risks associated with the treatment. The agency states that the letters “notify manufacturers of each such licensed product to update the package insert to include available information related to the risks and to update the Medication Guide for these products to identify the possibility of the increased risk of getting cancers, including certain types of cancers of the immune system.”1

Treatments required to have updated warnings include all FDA-approved CAR T-cell therapies and licensed BCMA-directed and CD19-directed genetically modified autologous CAR T-cell immunotherapies. The letter stating these requirements has been sent to the manufacturers of Abecma, Breyanzi, Carvykti, Kymriah, Tecartus, and Yescarta.1

Since the initial letters, the FDA has tweaked it's letter to Gilead regarding Tecartus, its CAR T treatment. Unlike the other therapies, it is no longer being listed as causing T cell malignancies.6

“Patients and clinical trial participants receiving treatment with these products should be monitored life-long for new malignancies,” the FDA wrote in a statement. “In the event that a new malignancy occurs following treatment with these products, clinicians are encouraged to contact the manufacturer to report the event and obtain instructions on collection of patient samples for testing for the presence of the Chimeric Antigen Receptor transgene.”

In November 2023, the FDA announced plans to investigate the potential risks of secondary cancer linked to CAR T-cell therapy. The agency made this decision based on reports of T-cell malignancies, including CAR-positive lymphoma, in patients who received treatment with BCMA- or CD19-directed autologous CAR T-cell immunotherapies. The reports were from clinical trials and adverse events (AE) data sources.2,3

In 2017, Novartis’ Kymriah was the first CAR T-cell therapy to receive FDA approval. Since that time, five more have been approved.4

Despite these risks, FDA spokesperson Carly Kemper told NBC News that the “overall benefits of these products continue to outweigh their potential risks.”4

At the 2023 American Society of Hematology annual meeting, City of Hope presented results of a study that tackled potential immunotherapies and personalized treatments aimed at preventing CAR T-cell therapy relapse and resistance.5

Some of their findings included:

  • Improving CAR T treatment for lymphoma.
  • Bispecific Antibody Combo showing potential for relapsed lymphoma.
  • Personalized vaccines attacking lymphoplasmacytic lymphoma.
  • Liso-Cel CAR T offers potential for resistant blood cancers.5

“The exciting findings presented at the ASH 2023 conference illustrate the exceptional science unfolding across a wide spectrum of hematologic malignancies and the welcome optimism these discoveries can bring to our patients,” said Eileen Smith, MD, Francis & Kathleen McNamara Distinguished Chair in Hematology & Hematopoietic Cell Transplantation, City of Hope, in a company press release. “City of Hope and our colleagues at Translational Genomics Research Institute and City of Hope Phoenix, Atlanta and Chicago continue to pursue advances that will enhance the survival and quality of life for people with blood cancers.”5

NOTE FROM THE EDITOR: This article has been updated to reflect revised safety demands to Gilead's Tecartus.


  1. FDA Roundup: January 23, 2024. FDA. January 23, 2024. Accessed January 24, 2024.
  2. FDA Investigating Risk of Secondary Cancers in Patients Administered CAR T-Cell Therapy. Pharmaceutical Executive. November 29, 2023. Accessed January 24, 2024.
  3. FDA Investigating Serious Risk of T-cell Malignancy Following BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies. FDA. November 28, 2023. Accessed January 24, 2024.
  4. FDA says cancer treatment CAR-T therapy may increase risk of cancer. NBC News. January 23, 2023. Accessed January 24, 2024.
  5. City of Hope scientists present promising new research at American Society of Hematology annual meeting. City of Hope. December 11, 2023. Accessed January 24, 2024.
  6. Gilead's Tecartus gets revised safety demand amid FDA's push for CAR-T boxed warnings. Fierce Pharma. January 24, 2024. Accessed January 25, 2024.
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