Delayed and subacute CAR T-cell toxicities (≥ 30 days post infusion)
| Toxicity . | Presentation . | Risk factors or alternate etiologies . |
|---|---|---|
| Immune effector cell–associated hematotoxicity | Generalized cytopenias (anemia, thrombocytopenia, neutropenia) with bone marrow hypocellularity and/or transfusion dependence Bimodal pattern of presentation | CRS severity Medication effects Viral or other infection Disease relapse Delayed IEC-HS |
| Immune reconstitution | B-cell aplasia Persistent hypogammaglobulinemia Recurrent infections (particularly sino-pulmonary) Vaccination responses (prior titers) | On-target, off-tumor targeting |
| Neurocognitive function | Difficult to assess without formal testing, which would need to be done prospectively. Changes may be subtle and not consistent across domains. | ICANS, severity and association with long-term outcomes unknown |
| Other end organs | Organ specific (eg, persistent cardiopulmonary compromise) | CRS severity and acute impact on end-organ function during event Site of extramedullary disease |
| Toxicity . | Presentation . | Risk factors or alternate etiologies . |
|---|---|---|
| Immune effector cell–associated hematotoxicity | Generalized cytopenias (anemia, thrombocytopenia, neutropenia) with bone marrow hypocellularity and/or transfusion dependence Bimodal pattern of presentation | CRS severity Medication effects Viral or other infection Disease relapse Delayed IEC-HS |
| Immune reconstitution | B-cell aplasia Persistent hypogammaglobulinemia Recurrent infections (particularly sino-pulmonary) Vaccination responses (prior titers) | On-target, off-tumor targeting |
| Neurocognitive function | Difficult to assess without formal testing, which would need to be done prospectively. Changes may be subtle and not consistent across domains. | ICANS, severity and association with long-term outcomes unknown |
| Other end organs | Organ specific (eg, persistent cardiopulmonary compromise) | CRS severity and acute impact on end-organ function during event Site of extramedullary disease |
CAR, chimeric antigen receptor; CRS, cytokine release syndrome; ICANS, immune effector cell–associated neurotoxicity syndrome; IEC-HS, immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome.