Post-CAR T-Cell Therapy:

CAR T-cell therapy represents one of the most exciting advancements in treating haematological patients with relapsed or refractory cancers. CAR T-cells, or Chimeric Antigen Receptor T-cells, are a form of immunotherapy in which a patient’s own T-cells are genetically modified to express a receptor (the chimeric antigen receptor) that can recognise and target cancer cells. Once these modified cells are re-infused into the patient’s body, they can seek out and destroy cancer cells with remarkable precision.

We are now entering an era where this innovative therapy is also being used to treat chronic, non-malignant haematological conditions such as thalassaemia and sickle cell disease. CAR T-cell therapy is based on gene modification, where specific genes are altered to target and destroy cancer cells. This revolutionary concept offers many patients the chance to survive otherwise aggressive diseases, especially those who have undergone multiple chemotherapies without achieving remission, such as those with acute lymphoblastic leukaemia. However, the management of toxicities such as cytokine release syndrome (CRS) and neurotoxicity remains a critical aspect of post-CAR T-cell care. These complications arise from the body’s complex immune response, which can be life-threatening if not properly monitored and managed. It is vital to carefully monitor patients and intervene promptly. Medications that interrupt the pathological immune activation—such as tocilizumab, an IL-6 inhibitor—are often used to manage CRS, as they can halt the immune overreaction while preserving the effectiveness of CAR T-cells.

Nevertheless, not all patients respond well to tocilizumab, and neurotoxicity is another significant concern. Symptoms such as tremors, parkinsonian changes, speech difficulties, memory and concentration problems, and even panic attacks and anxiety have been observed. This occurs because CAR T-cells can penetrate the blood-brain barrier, affecting the central nervous system. In these cases, the use of steroids is often unavoidable to stabilise the patient.

Fortunately, with improved monitoring and timely interventions, the majority of patients recover. However, other complications, such as pancytopenia or isolated thrombocytopenia, can arise post-CAR T therapy. The underlying cause is still unclear, but it may be related to prior chemotherapy or lymphodepletion therapy required before CAR T infusion. In severe cases, a rescue allogeneic stem cell transplant may be necessary. Some institutions even cryopreserve autologous stem cells before CAR T therapy to perform a rescue transplant in cases of prolonged cytopenia.

In my experience, these side effects can be incredibly challenging, as patients with prolonged cytopenia are at high risk of serious infections, which can sometimes prevent the possibility of a rescue transplant. In such cases, we unfortunately may lose the patient.

We are truly at the dawn of a new era in CAR T-cell therapy, and I am confident that, in the future, we will continue to improve treatment pathways and outcomes. A deeper understanding of the pathophysiological mechanisms within the human body is crucial to refining our therapies and enhancing patient survival.