Critical Care Management of Toxicities Associated With Targeted Agents and Immunotherapies for Cancer

Abstract

Objectives: To describe the most common serious adverse effects and organ toxicities associated with emerging therapies for cancer that may necessitate admission to the ICU.

Data sources and study selection: PubMed and Medline search of relevant articles in English on the management of adverse effects of immunotherapy for cancer.

Data extraction and data synthesis: Targeted therapies including tyrosine kinase inhibitors, monoclonal antibodies, checkpoint inhibitors, and immune effector cell therapy have improved the outcome and quality of life of patients with cancer. However, severe and life-threatening side effects can occur. These toxicities include infusion or hypersensitivity reactions, cytokine release syndrome, pulmonary, cardiac, renal, hepatic, and neurologic toxicities, hemophagocytic lymphohistiocytosis, opportunistic infections, and endocrinopathies. Cytokine release syndrome is the most common serious toxicity after administration of monoclonal antibodies and immune effector cell therapies. Most of the adverse events from immunotherapy results from an exaggerated T-cell response directed against normal tissue, resulting in the generation of high levels of proinflammatory cytokines. Toxicities from targeted therapies are usually secondary to "on target toxicities." Management is largely supportive and may include discontinuation of the specific agent, corticosteroids, and other immune suppressing agents for severe (grade 3 or 4) immune-related adverse events like neurotoxicity and pneumonitis.

Conclusions: The complexity of toxicities associated with modern targeted and immunotherapeutic agents for cancer require a multidisciplinary approach among ICU staff, oncologists, and organ specialists and adoption of standardized treatment protocols to ensure the best possible patient outcomes.

Figure 1.. CRS Grading and Management Considerations Associated with Immune Effector Cell Therapy

The major clinical manifestations of CRS are fever, hypotension, and hypoxia. The CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. The mainstays of treatment of grade ≥2 CRS are anti–IL-6 monoclonal antibodies (tocilizumab) and corticosteroids. Recommended dose of corticosteroids can vary among institutions and within protocols. Suicide and elimination genes are still experimental (–122).

Figure 2A.. ICANS Grading and Treatment Considerations

The grading of ICANS is determined by the most severe events (ICE score, level of consciousness, motor symptoms, seizures, and signs of elevated ICP/cerebral edema) not attributable to any other cause. Patients with grade 3 and 4 neurotoxicity should be monitored and managed in the ICU. Frequent neurologic examination and treatment of seizures and cerebral edema require close collaboration with neurology and neurosurgical consult services. Corticosteroids are indicated in patients with grade 3 and 4 neurotoxicity. Suicide and elimination genes are still experimental (–122).

Figure 2B.

Immune Effector Cell-Associated Encephalopathy (ICE) Score