CAR-T-Toxicity

Toxicities

• Cytokine release syndrome (CRS): fever, HoTN, shock secondary to overwhelming cytokine release from proliferating T cells
• Immune effector cell-associated neurotoxicitiy synd. (ICANS): cerebral edema → HA, aphasia, delirium, lethargy/obtundation. Graded using ICE score (vide infra).

CRS cytokine release syndrome

發燒、低血壓、呼吸變喘，嚴重者甚至可能昏迷 1 Fever (≥38°C) ± other sx 2 Fever + HoTN not needing pressors ± O2 by nasal cannula 3 Fever + pressor ± O2 > nasal cannula 4 Fever + >1 pressor ± ⊕ pressure vent

• Treatment : Supportive (fluids, O2), ± steroids ± anti-IL-6 (tocilizumab or siltuximab), depending on severity

ICANS cytokine release encephalopathy

僵化、不講話、沒反應，嚴重者可能眼睛看不見 1 ICE 7–9 pts 2 ICE 3–6 pts 3 ICE 0–2 pts 4 Unarousable & unable to perform ICE

• Management : Steroids, anticonvulsants for seizures

On target / on tumor：大家最期待看到的效果，針對腫瘤的治療。 On target / off tumor：原本要打白血病的標記分子 CD19，可是它不在腫瘤上，而是帶有 CD19 抗原的正常細胞遭受攻擊。 Off target / on tumor：歪打正著。 Off target / off tumor：沒打中白血病的標記分子 CD19，也沒打中腫瘤，屬於「脫靶效應」（off-target effects）的一種。