acute CAR-T cell therapy toxicities in adults

Overview

• chimeric antigen receptor T-cell (CAR-T) therapy is an advanced therapy medicinal product (ATMP) using immune effector cells (IEC)
• acute, early-onset toxicities typically occur within 30 days of infusion and carry high morbidity and mortality risks if recognition or management is delayed
• standard UK management follows national guidance developed by the Pharmacy ATMP Network UK (PAN UK) in collaboration with haematology specialists
• clinical grading across all UK CAR-T treatment centres utilizes the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading system

Main Clinical Indications

• relapsed or refractory B-cell acute lymphoblastic leukaemia (B-ALL)
• relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and other high-grade B-cell lymphomas
• relapsed or refractory mantle cell lymphoma (MCL)
• relapsed or refractory follicular lymphoma (FL)
• relapsed or refractory multiple myeloma (MM)

Key Acute Immune Effector Cell (IEC) Toxicities

Cytokine Release Syndrome (CRS)

• most common acute side effect, typically presenting within the first week following infusion
• clinical presentation ranges from mild constitutional symptoms to life-threatening multi-organ failure

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

• serious acute neurological toxicity, typically presenting within the first month after therapy
• manifestations include language disturbance, impaired handwriting, confusion, agitation, cerebral edema, and death

Immune Effector Cell–Hyperinflammatory Syndrome (IEC-HS)

• rare, severe hyperinflammatory state characterized by prolonged immune activation, overlapping clinically with secondary hemophagocytic lymphohistiocytosis (HLH)
• managed in accordance with ASTCT IEC-HS consensus recommendations

Clinical Monitoring and Management Principles

• regular monitoring for signs and symptoms of IEC toxicities must be performed according to individual Summary of Product Characteristics (SmPC) and national service specifications
• patients with suspected CRS or ICANS require frequent monitoring due to the risk of rapid clinical deterioration requiring organ support
• early intensive care unit (ICU) notification: the ICU team must be alerted for any patient with suspected CRS or ICANS, regardless of the NEWS2 score, allowing transfer earlier than standard NEWS2 escalation thresholds
• diagnostic uncertainty or management queries require immediate escalation to the attending consultant
• post-discharge planning: patients and carers must be advised on the risk of delayed side effects and provided with clear management plans prior to discharge

Scope Exclusions

• guidance does not cover non-IEC associated toxicities (such as lymphodepleting chemotherapy side effects, tumor lysis syndrome, or infections), late-onset toxicities (> 30 days post-infusion), or pediatric/adolescent pathways

Reference:

• NHS Specialist Pharmacy Service. Understanding acute CAR-T cell therapy toxicities in adults. Published October 2, 2026