Toxicities associated with CAR T-cell therapy

Treatment with CAR T cells has been associated with cytokine release syndrome, which can be life-threatening.[171,172] Cytokine release syndrome presents as fever, headache, myalgias, hypotension, capillary leak, hypoxia, and renal dysfunction. Severe cytokine release syndrome has been effectively treated with tocilizumab, an anti–interleukin-6 receptor (IL-6R) antibody.[171,173] Long-term persistence of CAR T cells can lead to B-cell aplasia, necessitating immunoglobulin replacement.[171]

Neurotoxicity, including aphasia, altered mental status, and seizures, has also been observed with CAR T-cell therapy, and the symptoms usually resolve spontaneously.[174] CNS symptoms have not responded to IL-6R–targeting agents or other approaches.

Other CAR T-cell therapy side effects include coagulopathy, hemophagocytic lymphohistiocytosis (HLH)–like laboratory changes, and cardiac dysfunction. Between 20% and 40% of patients require treatment in the intensive care unit, mostly pressor support, with 10% to 20% of patients requiring intubation and/or dialysis.[170,171,175,176] In one study, patients who developed HLH-like toxicities after CAR T-cell therapy had lower relapse-free survival (RFS) and OS rates than those who did not develop these toxicities (RFS rates, 25.7% vs. 57.6%; OS rates, 4% vs. 81%).[177]

For an extensive discussion of CAR T-cell toxicities and approaches to mitigate these toxicities, see Pediatric Chimeric Antigen Receptor (CAR) T-Cell Therapy.