How I treat HLH-like toxicities after immune effector cell therapy

Area of Science:

• Oncology
• Immunology
• Hematology

Background:

• Cancer immunotherapy advancements, including CAR T-cells, have introduced novel toxicities.
• Therapy-related hemophagocytic lymphohistiocytosis (HLH)-like toxicities are recognized as hyperinflammatory syndromes.
• Immune effector cell-associated HLH-like syndrome (IEC-HS) and CRS with multiorgan dysfunction (CRS-MOD) are distinct but challenging to differentiate.

Purpose of the Study:

• To outline a clinical approach for managing CAR T-cell-associated HLH-like toxicities.
• To differentiate between CRS-MOD and IEC-HS.
• To review current treatment strategies for these syndromes.

Main Methods:

• Clinical case review and expert consensus.
• Analysis of distinct clinical and temporal features of CRS-MOD and IEC-HS.
• Overview of diagnostic criteria and therapeutic interventions.

Main Results:

• IEC-HS emerges distinctly from CRS, often after resolution.
• CRS-MOD presents with HLH-like features during worsening CRS.
• Differentiating these syndromes is clinically challenging but critical.

Conclusions:

• Early recognition and intervention for HLH-like toxicities are vital for improving patient outcomes.
• Understanding the distinct pathophysiology of CRS-MOD and IEC-HS informs management strategies.
• A comprehensive diagnostic and therapeutic approach is essential for managing immunotherapy-induced hyperinflammatory syndromes.