The Food and Drug Administration (FDA) has mandated that all chimeric antigen receptor T-cell (CAR-T) therapies carry a boxed warning about the risk of secondary cancers. This decision comes after the agency’s review of post-marketing reports found that CAR-T treatments can cause secondary cases of leukemia and myelodysplasia.
Background on CAR-T Therapies
CAR-T cell therapy is a revolutionary new cancer treatment that involves genetically engineering a patient’s own T-cells to attack their cancer. The process involves:
- Collecting T-cells from a patient’s blood
- Genetically modifying the T-cells in a lab to produce special receptors on their surface called chimeric antigen receptors (CARs)
- Growing large numbers of these CAR-T cells
- Infusing the CAR-T cells back into the patient
Once infused back into the patient, the CAR-T cells multiply and work to identify and destroy cancer cells.
CAR-T therapy has shown extremely promising results for certain blood cancers like leukemia and lymphoma, with complete remission rates over 50% in some studies.
The first two CAR-T cell therapies – Kymriah and Yescarta – were approved by the FDA in 2017. There are currently six approved CAR-T products in the U.S. However, the treatments also come with significant side effects like cytokine release syndrome.
Reports of Secondary Cancers
Although CAR-T therapy has demonstrated powerful efficacy against blood cancers, there have been concerning reports of secondary cases of other cancers following treatment.
| CAR-T Therapy | Secondary Cancer Cases Reported |
|---|---|
| Kymriah | 5 cases of leukemia, 1 case of myelodysplasia |
| Yescarta | 7 cases of myelodysplasia |
These reports prompted the FDA to review the safety data on all approved CAR-T products.
FDA Review and Decision
On January 23, 2024, the FDA announced it was mandating a boxed warning about secondary malignancies on the labels of all six FDA-approved CAR-T cell therapies:
- Kymriah
- Yescarta
- Breyanzi
- Tecartus
- Abecma
- Carvykti
A boxed warning is the strongest warning the FDA requires.
The agency said they identified 32 reported cases of secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) across the different CAR-T products they reviewed. The cases occurred 9 months to 5 years after CAR-T treatment.
Although the number of cases is small compared to the total number of patients treated, the FDA decided the link was strong enough to warrant enhanced warnings given the serious, life-threatening nature of secondary cancers.
Impact and Reaction
Mandating boxed warnings is likely to have significant impacts for CAR-T manufacturers and cancer patients:
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Informed Consent: The warnings could lead doctors to more strongly consider risks versus benefits when prescribing CAR-T therapy. Patients will need to be informed of the small but serious risks prior to consenting to treatment.
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Clinical Practice: Doctors may increase follow-up monitoring for secondary cancers among CAR-T recipients. However, there are no standard screening guidelines yet for survivors of CAR-T therapy.
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Industry Sales & Research: The warning could negatively impact sales projections for CAR-T manufacturers. However, analysts say the long-term sales potential still appears strong given the transformative benefit CAR-T offers certain patients. Research into the biological mechanisms and possible prevention/mitigation of secondary cancers following CAR-T therapy is likely to expand significantly.
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Ongoing FDA Review: The FDA said they will continue to monitor reports of secondary cancers with CAR-T treatments. Further regulatory actions may be taken if new safety signals arise.
Patient advocates have argued the FDA should not over-warn about an innovative treatment that provides a last hope to many terminal cancer patients. However, agency officials say their duty is to properly inform patients and doctors of all known risks with medical therapies.
What’s Next
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More research is urgently needed to clarify the mechanisms by which CAR-T therapy might trigger secondary cancers, and determine if they can be predicted or prevented.
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Doctors will need to counsel patients on the risks and closely monitor them long-term after CAR-T treatment.
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The FDA will continue its safety monitoring and could take further actions in the future depending on what the accumulating evidence shows.
CAR-T therapy remains highly beneficial for many cancer patients who have run out of other options. However, the boxed warnings mandated by the FDA serve as an important reminder that more still needs to be learned about these powerful but complex treatments. Balancing efficacy and safety will be an ongoing challenge as the field works to maximize benefits and minimize risks.
To err is human, but AI does it too. Whilst factual data is used in the production of these articles, the content is written entirely by AI. Double check any facts you intend to rely on with another source.
