Preventing the Early-Phase CAR T Toxicities for B-Cell Lymphomas

The discussion focuses on preventive strategies for CAR T toxicities, with dexamethasone representing the most effective intervention. Based on ZUMA-1 data, dexamethasone 10 mg intravenously on days 0, 1, and 2 benefits patients with high baseline inflammation, elevated C-reactive protein, or significant disease burden. This prophylactic approach can significantly reduce high-grade toxicity risk for appropriately selected patients.

Lynch explains why prophylactic tocilizumab is not recommended despite seeming logical. As an IL-6 receptor antagonist, tocilizumab blocks peripheral receptors but causes serum IL-6 levels to rise dramatically. Since tocilizumab cannot cross the blood-brain barrier while IL-6 can, this leads to increased central nervous system (CNS) IL-6 exposure and potentially worse neurologic toxicity. When tocilizumab is used therapeutically for established cytokine release syndrome, concurrent dexamethasone helps mitigate CNS effects.

Dr Jacobson discusses anakinra (IL-1 receptor antagonist) studies, describing them as the Goldilocks story with conflicting results across 3 major studies. Memorial Sloan Kettering showed reduced high-grade neurologic toxicity, MD Anderson demonstrated decreased any-grade neurotoxicity without reducing high-grade events, while MGH showed no benefit. Despite limited preventive efficacy, anakinra remains the most effective treatment for immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome, a severe macrophage activation syndrome that can complicate CAR T therapy.