During this time, you may experience several side effects. The three major side effects your healthcare team will carefully watch for are:
- cytokine release syndrome
- neurotoxicity
- infection
Cytokine Release Syndrome 
Cytokines are proteins 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, and/or low oxygen level
- nausea, vomiting, diarrhea
- muscle or joint pain
- 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 with a medication called tocilizumab or a similar drug to manage this problem. Steroids or other medications may also be added.
If your cytokine release syndrome is very severe, you may need to be monitored in the intensive care unit.
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
Neurotoxicity, also called immune effector cell-associated neurotoxicity syndrome or ICANS, is inflammation in the nervous system. It occurs almost exclusively in patients who also had cytokine release syndrome, and is usually temporary.
Neurotoxicity typically occurs five to ten days after treatment, although it can occur later as well.
Symptoms of neurotoxicity may include:
- headaches, which may be severe
- difficulty speaking, slurred words, stuttering
- confusion/delirium
- difficulty staying awake
- dizziness
- difficulty paying attention
- loss of coordination
- weakness or shakiness (tremors)
- changes in handwriting
- seizures
- swelling in the brain
- memory loss
- hallucinations
- coma
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. You may also receive anti-seizure medication to protect you. In severe cases, you will be monitored and treated in the intensive care unit.
Although the symptoms of neurotoxicity can be frightening for you and your loved ones, 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.
Some patients have experienced delayed neurological problems with symptoms similar to those seen in patients with Parkinson’s disease. This problem is different than the neurotoxicity that occurs early after treatment. It is called delayed neurotoxicity or motor and neuro-cognitive toxicity (MNT).
Delayed neurotoxicity has been seen most often in patients who have myeloma but has also been seen in some lymphoma patients as well. Ask your treatment team if you are at risk for this side effect.
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 medications to reduce the risk of infection.
If you develop an infection, you may receive intravenous immunoglobulins (IVIG) infusions to help fight it.
It typically takes several weeks or months for your immune system to recover. However, it can also take longer.
At six months after CAR T-cell therapy, your doctor may recommend repeating many of the immunizations you received earlier in life.
Low Blood Counts
In addition to cytokine release syndrome, neurotoxicity, and infection, some patients experience prolonged low platelet, white blood cell, 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, like 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.
New Cancers
New cancers have been reported in some patients after CAR T-cell therapy, including rare T-cell lymphomas, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Talk to your doctor about whether you are at risk for developing one of these new cancers.
Other Rare Side Effects
Immune Effector Cell-Associated Hemophagocytic Syndrome (IEC-HS) is a rare but serious side effect reported in approximately 1% of CAR T-cell patients, although the incidence may actually be higher due to under-reporting. It is caused by a hyperactive immune system and is most often seen in patients who 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
- fever
- very high ferritin levels
- bleeding
Although other, less serious health problems can cause these symptoms, you should report them to your doctor immediately because prompt treatment of this condition is important. Steroids and other drugs such as anakinra and rituximab may help manage this complication.
Doctors are still learning about rare side effects after CAR T-cell therapy and how to treat them.
Next Page: Early Recovery
