Contrary to a warning placed on labels for CART-T cancer therapies, use of these treatments does not appear to boost the odds for a secondary cancer later, a new study shows.

Researchers at Memorial Sloan Kettering Cancer Center (MSKC) in New York City believe CAR-T may be safer in that regard than is now assumed, and warning labels may need to be revised.

The new data “do not suggest that there is an increased risk of second primary malignancies relative to other standard-of-care therapies,” said study lead author Dr Kai Rejeski, a visiting investigator and research fellow in the Adult Bone Marrow Transplant Service at MSKC.

“I worry that the warning labels may intimidate patients who receive this therapy, which may not be entirely founded,” Rejeski said in a news release from the American Association for Cancer Research.

According to the American Cancer Society, in CAR-T therapy, immune system T-cells “are taken from the patient’s blood and are changed in the lab by adding a gene for a receptor (called a chimeric antigen receptor or CAR), which helps the T-cells attach to a specific cancer cell antigen. The CAR-T cells are then given back to the patient.”

These supercharged T-cells are then able to target and destroy the specific type of cancer cell singled out by the antigen.

“This type of treatment can be very helpful in treating some types of cancer, even when other treatments are no longer working,” the ACS said.

However, in January the U.S. Food and Drug Administration acted on available data and placed a boxed warning on CAR-T therapies.

The warning advises that use of the treatment could raise a patient’s odds for later developing a new (secondary) T-cell cancer, one that isn’t related to the B-cell lymphoma or multiple myeloma for which the patients received CAR-T.

The warning was based on data from the FDA’s Adverse Event Reporting System.

However, Rejeski and others believe the FDA data does not take into account other patient risk factors that might be at play. Those factors include age, other treatments the patient might have received, and the length of patient follow-up.

“Patients are reading this in the news and, appropriately, asking questions to providers,” Rejeski explained. “We need to understand the potential risks, but at the same time, we need to interpret the data cautiously and contextualize it for our patients.”

In the new study, Rejeski and colleagues reviewed data from 18 clinical trials and seven “real-world” studies involving more than 5,500 patients with lymphoma or multiple myelomas.

Patients in the studies received one of six currently approved CAR T-cell therapies:

• Idecabtagene vicleucel (Abecma)

• Lisocabtagene maraleucel (Breyanzi)

• Ciltacabtagene autoleucel (Carvykti)

• Tisagenlecleucel (Kymriah)

• Brexucabtagene autoleucel (Tecartus)

• Axicabtagene ciloleucel (Yescarta)

Overall, 326 secondary cancers developed among the patients over a median follow-up period of just under 22 months. Overall, 5.8% of patients developed the new cancers.

Four of the trials compared outcomes for patients who received CAR-T therapy versus standard regimens. Rates of secondary cancers were similar regardless of treatment type: 5% of patients treated with CAR-T developed a new tumor compared to 4.9% of those who did not receive CAR-T.

Also, the risk of developing a secondary cancer did not change based on the type of cancer the patient was being treated for or the type of CAR-T therapy they received.

Patients who received more than three courses of non-CAR-T treatments before receiving CAR-T therapy did have a higher risk for a secondary cancer, compared to patients who got three or fewer such treatments, the researchers noted.

Furthermore, most of the new malignancies that arose during follow up were not T-cell specific, Rejeski’s team found.

Only five cases (0.09%) were T-cell malignancies. In three of these cases, malignant T-cells were tested to see if they had any genetic relation to the T-cells used in the patients’ CAR-T therapy. Only one such case tested positive, the researchers reported.

According to Rejeski, it’s also possible that CAR-T therapies are a victim of their own success: Patients are now living longer thanks to the treatments, giving new cancers more years in which to arise.

“CAR-T therapy is the first treatment in more than 20 years to show an overall survival benefit compared to the standard of care in refractory large B-cell lymphoma,” Rejeski noted.

His advice: “I would strongly caution against withholding this therapy because of the miniscule risk of developing T-cell malignancies,” he said.

The study was published Sept. 11 in Clinical Cancer Research.

More information

Find out more about CAR-T therapy at the U.S. National Cancer Institute.

SOURCE: American Association for Cancer Research, news release, Sept. 11, 2024

Source: HealthDay

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