CAR-T Therapies Cause Cancer? FDA Investigates Multiple Reports of Link
(Thursday, November 30, 2023)
This week FDA made an explosive announcement that there are reports of new cancers in patients treated with several approved CAR-T therapies. Although the FDA added the disclaimer that the benefit of these treatments still outweighs the risk of the same, the news is sure to rattle patients who received these treatments over the last 6 years since the first of these treatments were approved by the FDA.
CAR-T therapies have been presented as the last resort for patients with late-stage cancers. Since 2017, FDA has approved 6 CAR-T therapies and about 50,000 patients have been treated with these therapies. In addition, since the approval of the first CAR-T therapy, tens of thousands of patients have participated worldwide in more than 1000 clinical trials with new CAR-T therapies. Patients on CAR-T therapies have well-documented safety issues, which may or may not be related to the therapy. With the 6 FDA-approved CAR-T therapies, about 1 in 10 patients report serious adverse effects, there have been 1670 deaths, and 12 cases of T-cell lymphomas. According to the FDA, so far these numbers of adverse effects are acceptable due to the nature of the disease in the patients eligible for the CAR-T therapies.
It is important to consider these adverse events in the proper context. The CAR-T therapies are based on using lentiviral vectors that integrate into the genome which has been known for more than 20 years to potentially cause new cancers. The first gene therapy trials failed in 2003 primarily due to the incidence of secondary leukemia in patients who received similar treatment. In that trial, gene therapy to treat patients with X-linked severe immune deficiency disorder using retroviral vectors for inserting genes into bone marrow stem cells led to leukemia in 1 out of 11 of the patients in the trial. That led to the stoppage of all gene therapy clinical trials at that time. It took 15 years since then for the first CAR-T therapy to be approved after the risk was shown to be low, which appears to be the case with an incidence rate of about 1 in 4000.
From the regulatory point of view, the FDA would need to investigate these cases in the context of the patient populations to weigh the overall risk-to-benefit profile of CAR-T treatments, as announced by the FDA. For the CAR-T therapies approved by the FDA, there is not much the FDA can do if the risk-benefit profiles stay constant. The label for these treatments already carries the risk of secondary cancers. However, it is very likely that approval of future CAR-T treatments may have a higher burden of proof to demonstrate the risk assessment for secondary cancers with such therapies. While this FDA investigation may not derail the treatments already approved, for those under development, the path to approval seems to have become a little harder.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC