Adverse effects: What side effects of CAR T-cell therapy can occur and how are they managed?
Author: Julia Dobke, Editor: Maria Yiallouros, English Translation: Dr. med. Gesche Riabowol (geb. Tallen), Last modification: 2026/01/15 https://kinderkrebsinfo.de/doi/e217447
Table of contents
A body reacts to lymphodepletion and CAR T-cell administration (see chapter "Treatment process"): on the one hand, many cancer cells are quickly destroyed, which can lead to problems (such as tumour lysis syndrome), and on the other hand, the CAR T-cells can cause a severe immune reaction (cytokine release syndrome / cytokine storm). Also, neurological side-effects have been associated with this treatment strategy.
Tumour Lysis Syndrome
When many cancer cells are destroyed at the same time, tumour lysis syndrome can occur. In this case, the amount of cell components released into the bloodstream due to tumour cell decay exceeds the excretory capacity of the kidneys.
To prevent this, the following precautionary measures are taken: The patient receives a continuous (intravenously administered) infusion to ensure an adequate supply of fluids as well as drugs that help the kidneys excrete urine (diuretics such as furosemide). At the same time, a combination of other drugs are administered that reduce the consequences of cell decay in the body.
Cytokine Release Syndrome (CRS)
The Cytokine Release Syndrome (CRS) is a systemic inflammatory response that can occur as part of CAR T-cell therapy. It is characterised by a massive release of cytokines, which is triggered by the activation of white blood cells (leukocytes). Particularly severe courses are also referred to as cytokine storms.
To a certain extent, the occurrence of CRS after CAR T-cell administration is appreciated, as it is a sign of the efficacy of CAR T cells. However, if the reaction is overly severe, a life-threatening situation can develop that requires treatment in the intensive care unit.
In order to be able to detect the onset of CRS at an early stage, it is necessary for the patient to remain admitted to the hospital for at least 14 days after CAR T-cell administration, as CRS usually occurs a few days later. Blood values and vital signs are closely monitored.
(First) Signs of CRS
Signs of cytokine release syndrome (CRS) can include fever, increased heart rate, low blood pressure, rash, nausea, vomiting, or fatigue. In severe cases, the circulation becomes unstable, blood clotting disorders and breathing problems occur. Elevated cytokine levels are measured in the blood.
Treatment of CRS
The respective symptoms of cytokine release syndrome (CRS) are treated in a targeted manner, for example with antipyretic drugs, anti-nausea medication, administration of oxygen and circulatory stabilizing drugs. There is also a highly effective drug (tocilizumab) for the treatment of CRS. In particular, interleukin-6 (IL-6), a messenger substance in the blood that is important for the immune defence, is greatly increased in CRS. Tocilizumab prevents interleukin-6 from causing an inflammatory response in the body. This reduces or completely eliminates the symptoms of CRS.
Neurological side effects
Adverse effects affecting the central nervous system (CNS) can also occur after CAR T-cell therapy. These neurological side effects are often preceded by a cytokine release syndrome (see above). It is suspected that the cytokine interleukin-6 is also responsible for these neurological side effects. Central nervous system involvement is also known as CRES (CAR T cell-related encephalopathy syndrome) or ICAN (immune effector cell-associated neurotoxicity syndrome).
At the beginning, headaches, a general slowdown in activities and speech, confusion, fatigue and an altered handwriting can be signs of neurological involvement. If the symptoms intensify, speech disorders, visual hallucinations, mental confusion (delirium) and seizures can occur.
In any case, a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain should be carried out for clarification. If possible, a lumbar puncture should also be performed, furthermore an electroencephalography (EEG) to assess brain activity and the risk of developing seizures.
The treatment of neurological side effects is usually carried out by administering glucocorticoids such as dexamethasone or methylprednisone. An antiepileptic drug should be used for prophylaxis and treatment of seizures. Almost always, most symptoms regress completely, but in individual cases severe clinical courses with unfavourable outcomes do occur.
Haematological side effects
Bone marrow depression
All patients receive chemotherapy to reduce lymphocytes in the blood and in the bone marrow (lymphodepletion) prior to CAR T-cell administration. Since this reduces the function of the bone marrow, the number of blood cells can be reduced during the lymphodepletion phase itself, but especially after the administration of the CAR T cells.
This applies in particular to white blood cells (leukocytes) and their subgroup, the neutrophil granulocytes. Their number can be reduced over several weeks. As a result, patients have an increased risk of contracting an infection with bacteria, viruses or fungi. After being discharged home, parents should immediately contact the treating medical team if they have a low-grade fever or any other signs of infection. It should be ensured that the clinic can be visited immediately in less than two hours.
Red blood cells (erythrocytes) and/or platelets (thrombocytes) may also be low, so that replacement by blood transfusions may be necessary.
B-cell aplasia and immunoglobulin deficiency
The CAR T-cell products currently available in hospitals are directed against the surface protein CD19, which occurs on cells of B-cell leukaemia or B-cell lymphoma as well as on B cells in general, i.e. B lymphocytes. Hence, not only CD19-positive leukaemia or lymphoma cells, but also healthy, functional CD19-positive B lymphocytes are attacked and destroyed in the patient's organism.
B lymphocytes are responsible for the formation of antibodies [see antibody] against viruses and bacteria as part of a healthy immune defence. These antibodies or immunglobulins are necessary for the destruction of foreign viruses and bacteria (pathogens). If they are missing, there is a high risk of contracting severe infections.
In patients who have an immunoglobulin deficiency after CAR T-cell administration, the content of immunoglobulins in the serum must be checked regularly. Intravenous or subcutaneous administration of immunoglobulins may be required.
As a precaution, it is recommended that all patients should take medication that is effective against certain viruses and fungi in the first three months after CAR T-cell therapy in order to prevent infection at an early stage.