An anti-cancer miracle drug that costs millions may cause cancer?
At the end of November 2023, the U.S. Food and Drug Administration (FDA) issued an important announcement: for autologous CAR-T cell immunotherapies targeting BCMA or CD19, the FDA is investigating the serious risk of possible T-cell malignancies.
Entering 2024, the situation is becoming more and more severe. On January 22, the FDA issued an emergency notice requiring six marketed CAR-T cell therapies on the market to include a black box warning in the prescription instructions. This is not only a reminder to doctors and patients, but also a wake-up call that patients are at risk of T-cell malignancies after autologous CAR-T cell immunotherapy targeting BCMA or CD19.
The black box warning is the highest level of adverse reaction warning required by the FDA to label a drug. Once a black box warning is added, it means that the drug carries a significant risk of triggering a serious, even life-threatening reaction. This undoubtedly dropped a shock bomb on the hot field of CAR-T cell immunotherapy.
CAR-T therapy refers to chimeric antigen receptor T-cell therapy, which is a new type of cancer immunotherapy. The therapy uses the patient's own immune cells to genetically engineer T cells to recognize and attack tumor cells.
Market data shows that among the current CAR-T products approved for marketing in China, the lowest price is 999,000 yuan/needle, and the average price abroad is as high as 400,000 US dollars.
The advantage of CAR-T therapy is its ability to target specific tumor antigens, its greater lethality, and its long-term memory effect, which enables continuous removal of tumor cells in the body. Therefore, CAR-T therapy has achieved significant efficacy in the treatment of certain hematological malignancies (such as acute lymphoblastic leukemia and non-Hodgkin lymphoma), and is also being explored and applied in the treatment of other types of tumors.
1. Case review: What is the first batch of patients to use CAR-T therapy in China?
Aunt Qin, one of the first patients to use CAR-T therapy in China, was diagnosed with diffuse large B-cell lymphoma in 2017 and went through 12 rounds of chemotherapy without controlling the disease, and in November 2018, she chose CAR-T cell therapy under the advice of her doctor, which is the first batch of lymphoma patients in China to receive CAR-T therapy.
Although Aunt Qin also had side effects after receiving CAR-T treatment, such as fever, hand tremors, etc., these side effects are reversible, and doctors have ways to deal with these side effects, and Aunt Qin herself can accept these symptoms. After more than 40 days of hospitalization, Aunt Qin was successfully discharged.
As of August 2023, according to the "Health Times", Aunt Qin has achieved 5 years of cancer-free survival.
As more and more cancer patients receive CAR-T therapy, it is also relieving more and more problems.
2. Is CAR-T therapy an angel or a devil?
Memorial Sloan Kettering Cancer Center (MSKCC) reported a complete response rate of 83% for relapsed acute lymphoblastic leukemia refractory to CAR-T therapy, which is significantly better than chemotherapy.
CAR-T therapy is to construct a specific chimeric antigen receptor (CAR), transduce T lymphocytes to express CAR through gene transduction methods such as lentivirus or electroporation, and then expand these cells in vitro and then infuse them back into patients.
After the antigenic chimeric receptor on T cells is activated by the specific antigen recognized, it can transmit activation signals to the intracellular domain through the transmembrane region, causing cell activation and killing toxicity against target cells, and at the same time, accompanied by amplification signal transmission, causing a cascade amplification effect on target cell killing.
There are pros and cons to this process, which is that it has a strong killing effect on tumor cells, and the disadvantage is that this process leads to the release of large amounts of cytokines, causing cytokine release syndrome (CRS).
This is also the most common and serious adverse effect of CAR-T therapy in clinical practice, mild CRS is manifested by fever accompanied by fatigue, diarrhea, rash, joint and muscle pain, and in more severe cases, patients may develop hypotension, cardiac dysfunction, respiratory and circulatory failure, multi-organ system failure, and may progress to death if not treated in time or overreact.
At the same time, FAD's investigation revealed that the cancer risk of CAR-T therapy may stem from the viral vectors used to deliver cell and gene therapies, as the patient's own T cells are pumped and genetically modified to be able to identify cancer cells based on specific biomarkers, and while viral vectors can deliver genetic payloads, it can also cause cancer when viral vectors insert their own genetic material into a person's genome.
In particular, insertion in the vicinity of cancer-related DNA sequences or repressors may initiate transcription of cancer-related protein molecules.
3. Cancer is in an advanced stage, and treatment should be cautious
At present, CAR-T therapy is too expensive to be used as a treatment that ordinary people can afford, so what should ordinary people pay attention to if they have cancer?
1. Pain management: Patients with advanced cancer often experience severe pain, and doctors will formulate corresponding analgesic plans according to the degree and type of pain of the patient, which may include medication, radiation therapy or surgical intervention.
2. Nutritional support: Patients with advanced cancer often suffer from malnutrition, because tumors consume a lot of nutrients, and patients may have difficulty taking in food due to treatment side effects or tumors compressing the digestive tract. Therefore, nutritional support is essential to maintain the patient's physical strength and immune function.
3. Psychological support: Terminally ill cancer patients and their families often face tremendous psychological pressure, so psychological support and psychological counseling are equally important. A professional psychologist or counselor can help patients and families cope with anxiety, depression, and other psychological distress.
4. Hospice care: In the advanced stages of cancer, patients and families need to face the last stages of life. Hospice care includes symptom relief, comfort treatment, and support for patients and families to help them spend their final days with dignity. #Universal Life Guide##Headlines Tell the Truth##来点儿干货#