New research from the University of Pennsylvania and Stanford University finds no link between CAR-T cell therapies and the development of secondary T-cell malignancies.
At a joint event held by the Friends of Cancer Research and Parker Institute for Cancer Immunotherapy on Monday, cell therapy pioneer Carl June of the University of Pennsylvania Perelman School of Medicine revealed findings from a recent unpublished study from his group that looked at 783 patients who had received CAR-T treatments for HIV-1 or various cancers. Over more than 2,200 patient-years of observation, the group found 18 patients, or 2.3%, who developed secondary malignancies.
These secondary cancers arose a median of 1.94 years after CAR-T treatment, and most were solid tumors.
However, June said that none of these cases showed insertion of the CAR molecule, adding that the research group did not find enough evidence to attribute the secondary cancers to the CAR-T cell therapy.
In a separate study, also presented by June, researchers analyzed 725 patients who had been treated with CAR-T therapy at Stanford since 2016. Overall, 25 patients developed secondary primary malignancies, 11 of which were solid tumors, 13 were hematologic cancers and one was a T-cell lymphoma. In the lone T-cell malignancy case, the Stanford researchers found no evidence of insertion of the CAR transgene.
“Between Stanford and Penn and these unpublished studies, with 1,500 patients analyzed, there’s not a single case where the integrated vector transgene has been observed,” June said during the joint event, adding that caution is still warranted, especially when treating patients with extensive mutations before therapy and when using CAR-T therapies for non-malignant conditions.
Monday’s presentation comes after the FDA in November 2023 announced that it was looking into the safety of CAR-T therapies after it had flagged cases of secondary T-cell malignancies that arose after treatment with approved CAR-T products.
A few months later, in January 2024, the FDA called on the manufacturers of these treatments to amend their products’ boxed warnings to reflect this risk. The regulator formalized this call as an official requirement in April 2024.
All six commercially available CAR-T therapies were affected: BMS’s Abecma (idecabtagene vicleucel) and Breyanzi (lisocabtagene maraleucel), Gilead’s Tecartus (brexucabtagene autoleucel) and Yecarta (axicabtagene ciloleucel), Novartis’ Kymriah (tisagenlecleucel) and J&J’s Carvykti (ciltacabtagene autoleucel).
The FDA in January 2024 provided more details regarding its investigation, noting at the time that it had identified at least 22 cases of secondary malignancies potentially linked to CAR-T therapies. In three of the cases, the CAR transgene was found in a malignant clone.
