Investigation Into CAR-T Cell Treatments Reveals New Data on Patient Deaths, Effectiveness

Findings of new report come as FDA is reviewing potential CAR-T cell treatment side effects, amid reports of secondary cancers among patients with aggressive blood cancer.

A new study raises additional concerns about the safety and effectiveness of certain cancer treatments, known as chimeric antigen receptor T (CAR T) cell immunotherapies, indicating that certain patients may face an increased risk of serious adverse health outcomes, which can result in hospitalization or even death.

In findings published last week by the American Society of Hematology, a team of medical researchers analyzed data from the FDA Adverse Event Report System (FAERS) database, and found that individuals receiving CAR-T cell treatments face a significant risk of experiencing life-threatening side effects or die due to therapy-related complications.

While the treatments have been effective in improving health outcomes among patients with reoccurring or unmanageable multiple myeloma blood cancer, the medications Abecma (decabtagene vicleucel, or ide-cel), Carvykti (ciltacabtagene autoleucel, or cilta-cel), and Tecvayli (teclistamab) are known to cause a range of harmful side effects.

CAR T Cell Treatments Associated with Adverse Health Events

Researchers analyzed the data of 3,377 adverse reactions submitted to the FDA from 2019 to 2023. Among the complaints, 353 involved use of Carvykti , 496 involved Abecma, and 465 involved Tecvayli.

The most common side effects associated with the drugs included cytokine release syndrome (CRS), a toxic immune response; neurotoxicity, or damage the brain and nervous system; as well as immune effector cell-associated neurotoxicity syndrome (ICANS), a life-threatening form of neurotoxicity related to use of CAR T cell medications. Infections were another common complication found among the therapies.

According to the data, CRS was the most common adverse event reported, which affected 12.8% of the study participants, followed by ICANS, which affected 3% of the participants, and 1.9% developed non-ICANS neurotoxicity.

Abecma was associated with the highest risk of developing CRS and non-ICANS neurotoxicity following treatment, with 15.3% and 10.9% reporting they developed the conditions. Carvykti was associated with the highest risk of developing ICANS, and was also exclusively associated with the development of facial muscle paralysis.

Tecvayli treatments carried the highest risk of infection among the other CAR T cell immunotherapies, accounting for 23.7% of all reported infections.

The data also revealed that 225 of the complaints resulted in death. At least 189 deaths resulted from complications that were not related to cancer, accounting for 84% of the reported deaths.

Among the non-cancer related deaths, 88 involved Tecvayli, 59 were reported linked to Carvykti, and 42 were associated with Abecma.

Based on the findings, researchers concluded that CAR-T therapy is associated with increased risks of infection, CRS, ICANS, non-ICANS neurotoxicity, and death from life-threatening complications related to these conditions, compared to those who do not use this class of medications.

FDA CAR-T Cell Treatments Cancer Investigation

The study was published days after a recent announcement by the U.S. Food and Drug Administration on November 28, which indicated that the agency is investigating the risk that certain patients are developing new or more severe cancers after ending CAR T cell treatments.

The Car-T treatment investigation was initiated after officials become aware of several reports of secondary cancers among those with aggressive blood cancers, including multiple myeloma, lymphoma, and certain types of leukemia, after being treated with the drugs.

There are currently six FDA-approved CAR T cell therapy drugs, which were approved under the condition that a 15-year observational study be conducted to assess the potential for long-term adverse health conditions and secondary malignancies that could occur after treatment.

Officials are currently evaluating whether further regulatory action may be needed to address the health risks associated with the treatments.