In the first few weeks following the infusion of CAR T-cells, the cells will rapidly multiply in your body, building an army of cells to detect and fight cancer cells.
During this time, you may experience several side effects. Three major side effects your healthcare team will carefully watch for are:
- cytokine release syndrome (CRS)
- neurotoxicity (also known as ICANS)
- infection
Cytokine Release Syndrome (CRS)
Cytokines are proteins that are normally released by immune system cells to communicate with each other. When an army of CAR T-cells attacks cancer cells, they release a large number of cytokines into the body which can cause serious health problems. This is called cytokine release syndrome (CRS).
Cytokine release syndrome occurs in most patients after CAR T-cell therapy. It can begin within a few hours, days, or weeks after treatment. Symptoms may include:
- fever (100.4°F/38°C or higher)
- chills/shaking
- low blood pressure
- a low white or red blood cell count
- loss of appetite
- dizziness/lightheadedness
- fast or irregular heartbeat
- difficulty breathing/shortness of breath
- nausea, vomiting, diarrhea
- muscle or joint pain
- low oxygen levels
- swelling or fluid retention
- significant fatigue
Your healthcare team will give you IV fluids and/or medications to manage fevers, blood pressure changes, and oxygen if you have shortness of breath.
If the cytokine release syndrome is more severe, you may need to be treated in the intensive care unit and given a medication called tocilizumab (Actemra®) or a similar drug, to manage this problem. Steroids or other medications may also be added.
You will be closely monitored until all symptoms of cytokine release syndrome end. This usually takes a few days but can also take longer.
If not detected and treated promptly, cytokine release syndrome can be life-threatening.
Neurotoxicity (ICANS)
Neurotoxicity, also called immune effector cell-associated neurotoxicity syndrome or ICANS, is damage to the brain or nervous system. It may happen after CAR T-cell therapy and is usually temporary.
Neurotoxicity typically occurs a week or so after treatment, although it can occur later as well. It almost exclusively develops in patients who had cytokine release syndrome.
Symptoms of neurotoxicity may include:
- headaches, which may be severe
- difficulty speaking, slurred words, stuttering
- confusion/delirium
- anxiety
- difficulty staying awake
- dizziness
- difficulty paying attention
- loss of coordination
- weakness/shakiness
- changes in handwriting
- seizures
- swelling in the brain
- memory loss
- hallucinations
Depending on the severity of the neurotoxicity, your healthcare team may simply keep you comfortable until the problem resolves or give you medication to control it. The most common medication is steroids. In severe cases, you will be monitored and treated in the intensive care unit.
Although the symptoms of neurotoxicity can be frightening, they are usually fully reversible. However, it can take days, weeks, or even months for a patient to return to normal. In rare cases, neurotoxicity is life-threatening.
Infection
CAR T-cell therapy will reduce your white blood cell count, which weakens your immune system and increases the risk of infection. Until your immune system is functioning normally, you will be given antibiotics, anti-viral, and anti-fungal medications to reduce the risk of infection.
If you develop an infection, you may receive intravenous infusions of immunoglobulins (IVIG) to help fight it.
It typically takes several weeks or months for your immune system to recover. However, it can also take longer.
Low Blood Counts
In addition to cytokine release syndrome, neurotoxicity, and infection, some patients experience prolonged low platelet and red blood cell counts
Until your blood counts recover, you may need frequent, possibly weekly, transfusions of:
- blood and/or platelets
- growth factors -medicines that stimulate blood cell production
These problems usually resolve within a few weeks to months following CAR T-cell therapy. However, in some patients, these problems may persist for several years.
Fatigue
Fatigue after CAR T-cell therapy is very common and may take weeks or months to resolve. In some cases, it persists even longer.
Some patients need physical therapy to regain their strength, stamina, and stability. Safe exercise, such as daily walks, can also help build stamina and strength.
Anxiety, Depression
Anxiety, depression, and even post-traumatic stress disorder (PTSD) are common during treatment. It's stressful to go through cancer therapy, and CAR T-cell therapy is no exception.
For most patients, anxiety, depression, and PTSD improve three-to-six months after CAR T-cell therapy.
If you are experiencing anxiety or depression, ask the CAR T-cell center whether there is a mental health provider available who can help you. You can also consult BMT InfoNet's Directory of Mental Health Providers to find a mental health professional near you who can help you address your anxiety and concerns.
Other Rare Side Effects
Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) is a rare but serious side effect that occurs in approximately 1% of CAR T-cell patients. It is seen most often in patients who have had severe cytokine release syndrome. Symptoms include:
- an enlarged liver
- swollen lymph nodes
- skin rashes
- jaundice (yellow color on skin and in eyes)
- persistent coughing, difficulty breathing
- stomach pain, vomiting and diarrhea
- nervous system problems such as headache, trouble, vision changes or weakness
Although these symptoms can be caused by other, less serious health problems, you should report them to your doctor immediately because prompt treatment of HLH/MAS is important.
Patients with multiple myeloma have a small risk of delayed neurological problems that mimic Parkinson’s or Guillain-Barre disease. Symptoms include problems with balance, walking, and muscle tremors. The symptoms may last for several months. Notify your CAR T-cell therapy team immediately if you experience these problems.
