Secondary cancers after CAR-T therapy are very rare

The development of any type of second cancer after CAR T cell therapy is rare. This is indicated by an analysis of more than 400 patients treated at Penn Medicine. The US Food and Drug Administration (FDA) has been investigating 22 cases of T-cell cancers that occurred after CAR-T treatment, days after asking drug manufacturers drugs that added a serious warning to the label of their cancer therapies that use CAR-T technology. An article published in the New England Journal of Medicine noted that secondary malignancies have been reported with five of the six available CAR-T products and that the cancers included T-cell lymphoma, T-cell large granular lymphocytosis , peripheral T-cell lymphoma and cutaneous T-cell lymphoma. Standard Related News No The FDA issues a warning about the risk of cancer related to CAR-T therapies Reuters The rate is low and experts remind that the risk of secondary cancers is greater with standard chemotherapy Now, researchers at the Perelman School of Medicine at the University of Pennsylvania maintain that cases of a second cancer are rare. The team also described a unique case of incidental T-cell lymphoma that did not express the CAR gene and was found in the lymph node of a patient who developed a secondary lung tumor after CAR T-cell therapy. The University of Pennsylvania was a pioneer this treatment. More than 30,000 patients with blood cancers in the US, many of whom had few, if any, treatment options available, have been treated with CAR T-cell therapy since the first was approved therapy of this type in 2017. Some of the first patients treated in clinical trials have experienced long-lasting remissions of a decade or more. Related News standard No T cells, the fountain of youth R. Ibarra T cells, which are part of the immune system, can be reprogrammed to combat aging Secondary cancers, including T cell lymphomas, are a known and rare risk of several types of cancer treatment, including chemotherapy, radiation, and stem cell transplant. Currently, the therapy is only approved to treat blood cancers that have relapsed or stopped responding to treatment, so patients have already received many other types of treatment and face dire prognoses. With this issue, points out José María Moraleda, head of the Hematology Service at the Arrixaca Hospital in Murcia, you have to be very cautious. “It is true that there are some cases, but they are still very few and a very in-depth study of each case individually is needed.” For this expert from the Spanish Society of Hematology and Hemotherapy (SEHH), thanks to the genomic studies we have today, it is possible to discriminate quite reliably if this is the case, if it is a neoplasia secondary to CAR-T therapy. Although he recognizes that we must remember that the majority of these cases involve highly treated patients, so it is necessary to make “a risk-benefit balance.” That is, in each medical activity you have to say how many patients benefit. In November 2023, the FDA announced an investigation into several reported cases of secondary T-cell malignancies, including CAR-positive lymphoma, in patients who previously received CAR T-cell therapy products. Safety label In January 2024, the FDA began requiring drug manufacturers to add a safety warning label to CAR T-cell products. While the FDA review is still ongoing, it is still unclear whether the secondary T-cell malignancies were caused by CAR T-cell therapy. “When this case was identified, we did a detailed analysis and concluded that the T-cell lymphoma was not related to CAR T-cell therapy. As news of other cases came to light, we knew we needed to dig deeper and look at the cause.” our. data to better understand and help define the risk of any secondary cancers in patients who have received CAR T-cell products,” says senior author Marco Ruella, scientific director of the Lymphoma Program. Of 449 patients treated with CAR-T therapies available between January 2018 and November 2023, only 16 were diagnosed with a second cancer after receiving CAR T-cell therapy. The majority of secondary cancers (12 of 16) were solid tumors, including skin cancer, prostate cancer, and lung cancer. In a patient who developed a secondary lung tumor after CAR T cell therapy, an incidental T cell lymphoma was also identified in a lymph node removed during surgery for the lung tumor. Some of the first patients treated in clinical trials have experienced long-lasting remissions of a decade or more Molecular analyzes showed that the T-cell lymphoma did not harbor the CAR transgene, meaning it was not a CAR-positive lymphoma and there is no clear connection . with CAR-T therapy. These studies were made possible by the Penn Medicine Cell Therapy and Transplant Biobank, which facilitates the preservation of routinely collected samples and medical data for research purposes. For Moraleda it is very positive that regulatory agencies such as the FDA – the European Medicines Agency (EMA) said at the beginning that it was going to investigate the reported cases – are analyzing the situation. “It is their mission and it gives me peace of mind.” In Spain, all the available data is being collected and, at the moment, “fortunately we do not have any reported cases even with the non-commercial academic CAR-T.”