During this time, you may experience several side effects. The four major side effects your healthcare team will carefully watch for are:
- cytokine release syndrome
- neurotoxicity
- infection
- low blood counts
Cytokine Release Syndrome (CRS)
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 can occur 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 such as 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 is inflammation in the nervous system. The type of neurotoxicity typically seen early after CAR T-cell therapy is called immune effector cell-associated neurotoxicity syndrome (ICANS). It occurs most often in patients who had cytokine release syndrome.
ICANS typically occurs five to ten days after treatment, although it can occur later as well. It is usually a temporary side effect.
Symptoms of ICANS may include:
- headaches
- 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 ICANS, your healthcare team may simply take steps to keep you comfortable until the problem resolves or give you medication, such as steroids, to control it. You may also receive medication to protect you from seizures. 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, ICANS can be life-threatening.
Rarely, patients develop delayed neurological problems such as cranial nerve palsies which can cause facial weakness or drooping, and double vision. Very rarely, patients develop symptoms similar to Parkinson's disease such as tremors, stiffness, slow movement, or speech changes. These effects are called delayed neurotoxicity or motor and neuro-cognitive toxicity (MNT).
Delayed neurotoxicity has been seen most often in patients who have multiple 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 and antimicrobials to help fight it.
It typically takes several weeks or months for your immune system to recover. However, it can take longer. Once your immune system has recovered, your doctor may recommend repeating many of the immunizations you received earlier in life.
Low Blood Counts
Some patients experience prolonged low platelet, white blood cell, and red blood cell counts. Until your blood counts recover, you may need frequent 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 can also help build stamina and strength.
New Cancers
New cancers have been reported in some patients after CAR T-cell therapy, including skin cancer, rare T-cell lymphomas, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Discuss with your doctor whether you are at risk for developing one of these new cancers.
Other Rare Side Effects
A rare but very serious side effect called immune effector cell-associated hemophagocytic syndrome (IEC-HS) has been 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.
Immune effector cell-associated hemophagocytic syndrome (IEC-HS) may include:
- an enlarged liver
- swollen lymph nodes
- skin rash
- 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
Another rare side effect is immune effector cell colitis (IEC), which can cause very severe diarrhea.
Although other, less serious health problems can cause these symptoms, you should report them to your doctor immediately because prompt treatment of these conditions is essential.
Next Page: Early Recovery
