CAR-T for Multiple Myeloma
Multiple myeloma is a type of cancer that affects plasma cells in the bone marrow. Bone marrow produces three types of blood cells: white blood cells, red blood cells, and platelets. Plasma cells develop from B lymphocytes (B cells), which are a type of white blood cell involved in the body’s immune response. These plasma cells create antibodies that help protect us from infections and toxins.
Multiple myeloma begins when a plasma cell becomes abnormal and starts to divide uncontrollably. These abnormal plasma cells are called myeloma cells. As they multiply, they crowd out normal, healthy cells. Normally, plasma cells make up less than five percent of cells in the bone marrow, but in multiple myeloma, plasma cells increase to more than 10 percent.
The increase in abnormal plasma cells can lead to bone destruction and high calcium levels in the blood (hypercalcemia). Additionally, the large number of myeloma cells can interfere with the functions of other blood cells, especially red blood cells, which carry oxygen to tissues throughout the body.
As part of the immune system, plasma cells produce antibodies that fight infections and disease. However, in multiple myeloma, malignant plasma cells, or myeloma cells, produce an abnormal antibody called M protein (or monoclonal protein) and sometimes fragments called light chains, which accumulate in the blood and urine. This M protein does not aid in fighting infections; instead, it can thicken the blood and damage the kidneys. Since myeloma cells are typically distributed throughout the body, the disease is called multiple myeloma. However, “myeloma” and “multiple myeloma” are often used interchangeably.
The U.S. tracks cancer statistics closely. In 2020, there were 32,270 new cases of multiple myeloma, representing 1.8% of all new cancer cases in the United States. The five-year survival rate is 53.9%, and there are approximately 12,830 deaths from multiple myeloma each year, making up 2.1% of all cancer deaths.
CAR T-cell therapy has shown promising results in patients with multiple myeloma who have previously undergone at least three lines of standard treatment, including proteasome inhibitors, immunomodulatory drugs, and CD38 antibodies. The overall response rate to this therapy is 97%, with a complete response rate of 67% and a progression-free survival rate of 77%. The overall survival rate for these patients is 89%.
A study on CAR T-cell therapy has shown promising results in treating multiple myeloma:
- Out of 37 multiple myeloma patients treated, 35 (87%) responded positively to the therapy.
- Among these patients, 20 (57%) achieved complete remission within the first six months.
- For 18 patients with long-term follow-up (median follow-up time of 10 months), 13 (72%) remained relapse-free.
The study also notes that 85% of patients treated with CAR T-cells may experience cytokine release syndrome (CRS), a side effect caused by T-cell activation. However, the MMKTM has managed to keep CRS reactions mild (no higher than grade 2), which helps enhance the therapy’s cancer-fighting effects without severe adverse reactions.
The side effects of CAR T-cell therapy can vary depending on the specific technology and treatment protocol used. Different companies, both large and small, employ varying technologies, with newer generations of CAR T-cell therapies generally producing fewer side effects than the earlier versions.
The most notable side effect of CAR T-cell therapy is Cytokine Release Syndrome (CRS), a potentially severe reaction often linked to this type of treatment. CRS occurs when CAR T-cells multiply within the body and release cytokines (chemical messengers that support T-cell function) while targeting cancer cells. Symptoms of CRS can range from mild, flu-like symptoms to more severe reactions. Common symptoms include:
- Nausea
- Fatigue
- Headache
- Chills
- Fever