CAR-T Cell Therapy Cancer Risks May Drop Off After Two Weeks of Therapy: Study

Earlier this year the FDA required six CAR-T drug manufacturers to add secondary cancer warnings to drug labeling, and recommended life-long cancer screenings for patients.

New research indicates that more efficient treatment methods are available for patients undergoing CAR-T cell therapy, suggesting that current FDA guidelines mandating that patients remain close to treatment centers for four weeks after receiving the therapy results in unnecessary challenges and additional medical costs.

In a study published in Blood Advances on July 23, researchers monitored the outcomes of patients treated with specific CAR-T cell therapies for B-cell non-Hodgkin lymphoma, including axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel).

According to the findings, extending close monitoring of patients for four weeks appears to be an unnecessary precaution, as incidents of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are very uncommon after the first two weeks post-therapy.

CAR T-cell Therapy and Cancer Risks

CAR-T cell therapy is a method for fighting cancer that involves genetically modifying T cells (a type of white blood cell) in a lab to make those cells pinpoint and attack cancer cells. The therapy is often used to treat certain lymphomas, leukemias, and multiple myeloma.

While CAR-T cell therapy has been found to be an effective treatment method, concerns about the safety emerged earlier this year, after the U.S. Food and Drug Administration (FDA) warned about 22 cases of secondary cancer linked to CAR T treatments, prompting the agency to require several manufacturers to add black box warnings to all CAR-T drugs, indicating that the side effects may increase the risk of T-cell malignancies, which can result in hospitalization and death.

The FDA required new the black box warnings be added to Carvykti, along with Abecma (idecabtagene vicleucel), Breyanzi (lisocabtagene maraleucel), Kymriah (tisagenlecleucel), Tecartus (brexucabtagene autoleucel), and Yescarta (axicabtagene ciloleucel).

“As of December 31, 2023, the FDA had become aware of 22 cases of T-cell cancers that occurred after treatment with CAR-T cell products,” FDA officials wrote in a Perspective piece in the New England Journal of Medicine in January 2024. “Such cancers have included T-cell lymphoma, T-cell large granular lymphocytosis, peripheral T-cell lymphoma, and cutaneous T-cell lymphoma.”

As a result of the risks associated with side effects of Carvykti and other CAR-T cell treatments, the FDA recommends that patients or clinical trial participants receiving these treatments be monitored closely in the weeks following treatment, and regularly for the rest of their life by a health care professional for new cancers that may develop.

Patient Monitoring After CAR T-cell Therapy

However, this recently published study offers a different perspective on protocols for patient monitoring following treatment. Conducted by researcher Nausheen Ahmed and her team at the University of Kansas Cancer Center, the retrospective study analyzed 475 patients at nine medical centers from 2018 to 2023 who received infusions of axi-cel, tisa-cel, and liso-cel.

The findings indicate that severe side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were rare after the first two weeks post-therapy, incidences of CRS seldomly occurred after two weeks, and ICANS cases were rare in the third week.

These results suggest that the FDA’s current requirement for patients to stay near treatment centers for four weeks may be excessive, as extended monitoring may not be necessary for all patients.

However, after four weeks post-treatment, the greatest risk observed following CAR T-cell therapy was infections. Ahmed’s findings suggest that infections are the main cause of complications after the first month post-infusion, which indicates a need for ongoing vigilance against infections during this period.

The authors indicate that the existing supervision period could be reduced by half for some patients, which could alleviate financial and logistical burdens for patients and families from diverse socioeconomic backgrounds.

“This study provides valuable insights into optimizing CAR T therapy monitoring” researchers wrote. “And our findings may provide a framework to reduce physical and financial constraints for patients.”