CAR-T – A therapy that causes or cures cancer?

In the pursuit of finding a cure for certain diseases, it has been found that some drugs can be more harmful than the disease itself. Unfortunately, there have been instances in the history of medicine where certain drugs, such as the use of mercury for treating syphilis in the 16th century and the thalidomide catastrophe of the 60s, have resulted in unpredictable and serious consequences, including malformations in newborns and death. While stricter regulations successfully minimize harmful side effects, the ongoing FDA investigation into CAR-T therapy highlights the need for constant safety assessments of medical innovations.

FDA investigation

10 days ago, the FDA started investigating CAR-T therapy, an immunotherapy used to treat malignant diseases. This investigation was prompted by 19 reports stating that patients who received CAR-T therapy developed secondary malignant diseases and cancers. Essentially, these patients were diagnosed with another form of cancer while being treated for their primary one. The agency’s report states that patients treated with multiple products from the same class develop tumors of T-lymphocytes, which are white blood cells responsible for destroying foreign cells in our body.

CAR-T immunotherapy

CAR-T therapy is a chimeric antigen receptor therapy that modifies the patient’s immune cells to detect and attack the tumor cells. The main carriers of cellular immunity, T lymphocytes, also known as white blood cells, are first isolated from the patient’s blood, genetically modified in vitro, cultured, and then reintroduced into the patient’s bloodstream. Receptors on the surface of T lymphocytes are modified by adding domains for specific tumor epitope recognition and T lymphocyte activation. The most common method of introducing new receptors for tumor recognition is by using viral vectors that insert genes into specific locations in the genome.
After completing genetic changes, reintroduced and modified T lymphocytes can recognize and attack tumor cells. The first CAR-T therapy was approved in 2017, which means that it has been in use for 6 years. While the therapy has proven to be highly effective in treating leukemia and lymphoma, it has shown less efficacy in treating solid tumors.

Cancer as a side effect

It has been proven that the risk of acquiring a secondary malignant disease applies to all currently approved CAR-T immunotherapies that target the B-cell maturation antigen (BCMA) or CD19, two proteins expressed on the malignant B cells of our immune system. The assumption is that the modified retrovirus vector used for introducing receptors can cause genetic mutations that are responsible for cancer development. The agency recommends life-long monitoring for patients and clinical trial participants undergoing this therapy in case of secondary disease development.
It is important to note that the risk of secondary disease development is stated as a warning for this class of drugs. However, some patients from the reports were hospitalized or even died, so regulatory measures are being considered.

Oncologists consider this form of therapy disappointing to single out as riskier than others, as the frequency of side effects is low!

Responsibility of CD19 CAR-T immunotherapy manufacturers

The representatives of CAR-T immunotherapy manufacturers, Novartis, Gilead, and Bristol Myers Squibb, are using strict measures to monitor and report any harmful events to regulatory bodies. They are fully cooperating with the agency’s requests for data analysis regarding this investigation. The manufacturers have no evidence for the correlation between using the therapy and secondary disease development. The data is based on several tens of thousands of patients, and even showcased cases of T-cell secondary disease development without the use of CAR-T therapy.

Is the risk worth it?

Drug side effects can be mild, moderate, severe, and lethal, causing death directly or indirectly. The importance of CAR-T therapy is undeniable, as it has changed the course of treatment for patients with malignant diseases, but the severe side effects caused by other means of therapy are also not up for debate. The FDA advises against discontinuing therapy or avoiding starting it altogether. Patients should always follow their doctor’s and pharmacist’s instructions, putting aside the potential side effects. It’s crucial to monitor side effects while acknowledging the benefits of innovative therapy when treating challenging health concerns.

translated by: Lara Mužević