The American Society of Clinical Oncology (ASCO) released a guideline for managing immune-related adverse events from chimeric antigen receptor T-cell (CAR-T) therapy, which were published in the Journal of Clinical Oncology.
CAR-T therapy is used to treat several hematologic neoplasms by modifying T-cells to target malignant cells. The modified T-cells are typically delivered in a single infusion. CAR-T therapy is regarded as a living drug, and its effect persists long-term, potentially for decades.
However, the treatment is associated with severe toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which can be fatal. CRS occurs in 57% to 93% and ICANS in 20% to 70% of patients undergoing CAR-T therapy.
The ASCO guideline recommends grading CRS toxicities on a scale of 1 to 4, ranging from fever with no attributable cause and no hypotension or hypoxia (grade 1) to fever with hypotension requiring multiple vasopressors and/or hypoxia requiring positive pressure. Management should include antipyretics, intravenous hydration, and tocilizumab. Patients with grades 3 or 4 CRS should be admitted to the intensive care unit, be assessed for cardiac function, and treated with dexamethasone. Patients with grade 4 CRS should be treated with methylprednisolone.
ICANS toxicity ranges from immune effector cell-associated encephalopathy (ICE) score 7 to 9 with no depressed consciousness (grade 1) to ICE score 0; coma; life-threatening prolonged seizure; and/or diffuse cerebral edema, decorticate posturing or papilledema, cranial nerve VI palsy, or Crushing triad (grade 4). Management includes tocilizumab, dexamethasone, methylprednisolone, corticosteroids, and transfer to the intensive care unit, depending on grading and CRS status.
The guideline emphasized the importance of early detection of toxicities to enable prompt intervention due to a potential for patients to decline rapidly. As data about CAR-T therapy continue to evolve, recommendations will be routinely updated.
Santomasso BD, Nastoupil LJ, Adkins S, et al. Management of immune-related adverse events in patients treated with chimeric antigen receptor T-cell therapy: ASCO Guideline. J Clin Oncol. 2021;39(35):3978-3992. doi:10.1200/JCO.21.01992