CAR-T cell therapy is an innovative cancer treatment using a patient’s own genetically modified immune cells to fight cancer. While promising for certain blood cancers, it carries potential risks. This article explains the possible adverse events associated with this advanced therapy.
Acute Side Effects
Patients undergoing CAR-T cell therapy often experience immediate risks after infusion. The two primary acute toxicities are Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), both arising from robust immune system activation.
CRS is a common side effect where activated CAR-T cells release inflammatory proteins called cytokines into the bloodstream. This “cytokine storm” can lead to systemic inflammation, affecting various organs. Symptoms can range from mild, flu-like symptoms like fever and fatigue, to severe manifestations such as low blood pressure, difficulty breathing, and organ dysfunction.
ICANS involves neurological effects that can occur alongside or independently of CRS, related to the immune response affecting the central nervous system. Symptoms include headaches, confusion, difficulty speaking, tremors, and in severe cases, seizures or loss of consciousness. These acute toxicities typically manifest within the first few weeks, with most severe cases occurring within two weeks.
Additional Serious Complications
Beyond CRS and ICANS, other complications can emerge in the weeks following CAR-T therapy. Hematologic toxicities, or issues with blood cell counts, are common. Patients may experience prolonged cytopenias, meaning low levels of blood cells like neutropenia, thrombocytopenia, and anemia. These low counts can persist for weeks or months, increasing the risk of bleeding and fatigue.
The immunosuppression from CAR-T therapy and preceding chemotherapy significantly increases infection risk. Patients are vulnerable to bacterial, viral, and fungal infections, especially in the initial weeks and months. Infections are a leading cause of non-relapse mortality. CAR-T therapy can also lead to organ toxicities affecting the heart, kidneys, or liver, though these are less common than CRS, ICANS, and hematologic issues.
Long-Term Health Considerations
Long-term health considerations can manifest weeks, months, or years after CAR-T therapy. Persistent cytopenias, or low blood counts, remain a concern for some patients, potentially lasting for extended periods and necessitating continued monitoring and supportive care.
While acute ICANS typically resolves, some patients may experience delayed or persistent neurological effects, such as difficulties with memory, attention, or language. These can impact quality of life.
A rare but serious theoretical risk involves secondary malignancies, including T-cell lymphomas. The FDA is investigating rare cases of T-cell malignancies containing the engineered CAR gene. Long-term follow-up is crucial to monitor for such delayed complications.
Monitoring and Managing Risks
Healthcare teams employ comprehensive strategies to monitor and manage CAR-T cell therapy risks. Patients are typically admitted to specialized medical centers for close observation, especially during the first few weeks post-infusion when acute toxicities are most likely. Monitoring includes frequent vital sign checks, neurological assessments, and regular blood tests to track inflammatory markers and blood cell counts.
Specific medications are used to manage adverse events. For Cytokine Release Syndrome, tocilizumab, an anti-interleukin-6 receptor antagonist, is often administered to dampen the immune response. Corticosteroids, such as dexamethasone, are the primary treatment for Immune Effector Cell-Associated Neurotoxicity Syndrome, reducing brain inflammation.
Supportive care measures include transfusions for prolonged cytopenias and antibiotics or antiviral medications to prevent or treat infections. A multidisciplinary team, involving oncologists, neurologists, intensivists, and infectious disease specialists, ensures coordinated and timely management of these complex side effects.