CAR T-cell therapy is a form of immunotherapy in which patients’ T cells are modified to become better at tracking down and destroying tumor cells. CAR T cells are made by extracting thousands of a patient’s T cells, sending them to a lab where they’re outfitted with genes and proteins that improve their cancer-fighting prowess, and then re-infusing them into the patient.
Therapies using CAR T cells are being tested in several clinical trials, primarily in patients with B cell malignancies such as acute lymphoblastic leukemia and non-Hodgkin lymphoma and in some patients with solid tumors such as glioblastoma brain tumors.
CAR T-cell therapy can trigger a range of side effects, many of which begin subtly but can rapidly worsen. A particularly severe complication is cytokine release syndrome (CRS), also known as a cytokine storm. Once they enter the body, CAR T cells initiate a massive release of proteins called cytokines, which summon other elements of the immune system to join the attack on tumor cells. The resulting onslaught can produce dangerously high fevers, extreme fatigue, difficulty breathing, and a sharp drop in blood pressure. The condition tends to be especially severe in patient with extensive cancers.
CRS tends to arise within one to five days of the CAR T cells’ infusion into the patient, although it may occur weeks later in some cases. For most patients, the condition is mild enough that it can be managed with standard supportive therapies, such as acetaminophen and intravenous fluids.
In many cases, CRS is followed by a second wave of side effects that involve the nervous system, according to Dana-Farber’s Caron Jacobson, MD, clinical director of the Institute’s Cellular Therapies Program and a leader of clinical trials of CAR T-cell therapy for patients with treatment-resistant large B-cell lymphomas. These problems can include tremors, headaches, confusion, loss of balance, trouble speaking, seizures, and sometime hallucinations. While the causes of the symptoms are not well understood, the symptoms generally subside in a few days, although they can last for weeks in some cases. Extreme cases may be managed with steroids.
Patients usually stay in the hospital for at least a week after CAR T-cell infusion, or until the side effects subside (generally around two weeks). Although the risk of a recurrence of symptoms is low, they do sometimes arise, so clinicians monitor patients and stay in communication with them after hospital discharge.