Within a large group of more than 700 patients treated with CAR T cell therapy, researchers found no evidence that the therapy itself caused any type of secondary cancer in the modified T cells, according to new analysis reported in Nature Medicine from the Perelman School of Medicine and Penn Medicine’s Abramson Cancer Center. The rare occurrences of secondary cancers that did occur following CAR T cell therapy could be attributed to a damaged immune system from first-line cancer treatments like radiation and chemotherapy, but none of the cases in this group were caused by the treatment that alters cancer-associated genes in the patients’ T cells.
“These findings bolster previous Penn research demonstrating the safety of CAR T cell therapy,” says co-senior author Joseph Fraietta, an assistant professor of microbiology. “Penn’s robust patient samples and follow-up protocols allowed us to analyze not only whether patients who received CAR T cell therapy developed cancer after treatment, but to examine the cancer in those individuals at the cellular level to verify the science of why these cancers occurred.”
In late 2023, the FDA announced that they were investigating several reported cases of secondary T cell malignancies in patients who previously received CAR T cell therapy products.
For this study, researchers analyzed samples from 783 adult and pediatric patients from Penn Medicine and Children’s Hospital of Philadelphia who were treated with CAR T cell therapy in clinical trials and found 18 cases of secondary cancers. None of the 18 cases showed evidence that they were caused by insertional mutagenesis.
The researchers attributed the rare occurrence of secondary cancers to the suppression of the immune system from prior cancer treatments.
“It typically takes multiples factors causing changes at the cellular level for cancer to develop and grow,” says co-senior author, Frederic Bushman, the William Maul Measey Professor and Chair of Microbiology at Penn. “As we continue to evaluate larger cohorts of individuals treated with CAR T cell therapy, there is a chance we find an exception. However, the evidence continues to reassure us that the benefits of CAR T cell therapy far outweigh the risks.”
Read more at Penn Medicine News.
