Actemra (tocilizumab), an arthritis medication implicated in at least 1,100 patient deaths, has won FDA approval for the treatment of what is known as CAR-T cell-induced cytokine release syndrome. “CAR-T” is short for “Chimeric Antigen Receptor T-Cell.” CAR-T therapy is a new, sophisticated treatment for leukemia that shows great promise – but there is a serious, possibly fatal side effect, which Roche and Genentech believe can be mitigated by administering Actemra to the patient.
Before going further, here is a simplified explanation of CAR-T therapy. For many years, the “Holy Grail” of cancer research has been to find a way to turn the body's own immune system against malignant cells. This has been problematic, as cancer cells are essentially the body's own cells that have stopped dying off as cells normally do. Instead, they continue to grow and multiply until they kill the host body.
Because they are essentially native cells that have run amok, the immune system does not recognize them as foreign pathogens or a disease caused by outside causes (bacteria or viruses). Research for the past several years has focused on ways to get antibodies and killer T-cells to attack cancer cells in the same way they do other disease cells such as the flu or chicken pox.
CAR-T therapy is the most recent breakthrough in this type of immunotherapy for cancer. A blood sample is taken from the patient and T-cells are extracted. Those T-cells are then re-engineered and modified at the genetic level, essentially “training” them to recognize and destroy cancerous tumors.
These modified T-cells are known as “chimeric antigen receptor” or CAR-T cells. They are then grown and allowed to reproduce until there are several million of them. After this, they are injected back into the patient, where they continue to multiply and hopefully, seek out and destroy cancerous cells. Because these modified T-cells remain in the body after therapy is completed, they continue to protect the body from a recurrence of cancer, so remission is a common result.
That's the good news. The bad news is that once these CAR-T cells start killing cancer cells, they don't always stop there. The immune response goes into overdrive. T-cells communicate with other parts of the immune system by the release of chemicals known as “cytokines.” These cytokines instruct other cells on what action to take when confronted by a pathogen.
When cytokines get loose and begin circulating in the bloodstream, the result is cytokine-release syndrome, sometimes known as a “cytokine storm.” Basically, the body starts attacking itself. Symptoms manifest as high fever, swelling, nausea, fatigue, rapid heartbeat, skin rash and dangerously low blood pressure. In some cases, particularly when a patient is already compromised, the results can be fatal.
Until now, there has been no reliable treatment for CAR-T induced cytokine release syndrome. While clinical studies have shown that Actemra is effective in managing the condition, the medication is also linked to other potentially deadly side effects that include elevated LDL (“bad”) cholesterol, leading to an increased risk of heart attack and stroke. Currently, Roche and Genentech are facing an onslaught of litigation over patients deaths attributed to the medication, which has been prescribed for rheumatoid arthritis and a number of “off-label” indications.
It remains to be seen if this new treatment for cytokine-release syndrome is worth the risks to leukemia patients. Much will be based upon the actual effectiveness of Actemra in treating CAR-T.