In this podcast, special guest Matt McKenzie, PharmD, BCCCP, discusses various aspects of immunotherapy, including CAR-T cell therapy, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune checkpoint inhibitors. The episode also highlights the complexity of immunotherapy guidelines, challenges in symptom identification, grading scales for CRS and ICANS, adverse effects of HLH in immunotherapy, and the evolving nature of the topic.
CAR-T cell therapy is a form of immunotherapy that uses genetically engineered T cells to target cancer cells.
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are common side effects of CAR-T cell therapy.
Treatment options for CRS and ICANS include the use of steroids, anakinra, and tocilizumab.
Deep dives
Immunotherapy and CAR-T Cell Therapy
Immunotherapy, specifically CAR-T cell therapy, uses the body's immune system to fight cancer cells. CAR-T cells are genetically engineered T cells that target cancer cells and are infused back into the patient. The therapy can cause side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS is the most common and severe adverse event, characterized by fever, hypotension, and hypoxia. Treatment for CRS includes steroids and the use of tocilizumab. ICANS typically occurs after CRS and presents with neurological symptoms like encephalopathy and seizures. Steroids and anakinra are used for management. Other adverse events like secondary HLH and movement and neurocognitive treatment-emergent adverse events (MNTs) can also occur.
Mechanisms and Grading of CRS and ICANS
CRS occurs due to the activation of CAR-T cells, leading to the release of cytokines and chemokines. Grading of CRS ranges from 1 to 4 based on symptoms like fever, hypotension, and hypoxia. ICANS is characterized by the disruption of the blood-brain barrier and the accumulation of cytokines and CAR-T cells in the CNS. Grades 1 to 2 ICANS can be monitored on the floor, while grades 3 to 4 require ICU admission. Steroids and anakinra are commonly used for the treatment of both CRS and ICANS. EEG monitoring helps detect non-convulsive status epilepticus, and seizure prophylaxis is initiated for 30 days after CAR-T cell infusion.
Treatment Strategies for CRS and ICANS
Treatment strategies for CRS include tosylicumab, steroids, and anakinra. Tosylicumab can be given every 8 hours for grades 2 to 4 CRS. Steroids are used starting from grade 1 CRS, and higher doses are given for more severe cases. For ICANS, steroids and anakinra are the mainstay of treatment. Steroids are started in grade 1 ICANS, and anakinra is considered for steroid-refractory cases in grades 2 to 4. The use of anakinra as prophylaxis remains under investigation. Other interventions, such as seizure management and monitoring of cerebral edema, may be necessary.
Differences and Similarities between CAR-T Cell Therapy and Immune Checkpoint Inhibitors
CAR-T cell therapy and immune checkpoint inhibitors both aim to modulate the immune system to fight cancer. However, the mechanisms differ. CAR-T cells are genetically engineered T cells that directly target cancer cells, while immune checkpoint inhibitors are monoclonal antibodies that block inhibitory signals on T cells, allowing them to attack cancer cells. Adverse events from immune checkpoint inhibitors, such as cytokine release syndrome, can resemble those of CAR-T cell therapy. However, the mechanisms and direct effects on the immune system differ between the two therapies.
Main Idea/Key Point 1
Immunotherapy, including CAR-T cell therapy and immune checkpoint inhibitors, is becoming increasingly important in cancer treatment. It is crucial for healthcare professionals to familiarize themselves with these agents and the toxicities they can cause. Effective monitoring and treatment systems should be in place to ensure patient safety and optimal outcomes. Tocilizumab is the primary treatment for CAR-T cell-induced cytokine release syndrome (CRS), and early recognition and management are essential.
Main Idea/Key Point 2
Immune-related adverse events can affect multiple organ systems and can occur at any time during or after treatment with immune checkpoint inhibitors. Skin, GI tract, and lung toxicities are among the most common, and the use of these inhibitors is expected to expand, leading to more patients requiring ICU care. Prompt recognition, identification, and management of immune-related adverse events are crucial, with treatment options including steroids and targeted therapies. Effective communication and collaboration among healthcare teams, including critical care pharmacists, are essential in ensuring patient safety and positive outcomes.
