Clinical efficacy of anakinra to mitigate CAR T-cell therapy–associated toxicity in large B-cell lymphoma

Despite unprecedented efficacy, 1 the use of axicabtagene ciloleucel (axi-cel) for the treatment of patients with relapsed or refractory large B-cell lymphoma (LBCL) remains associated with acute toxicity, such as grade $3 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), occurring in 11% and 32% of patients, respectively. 2 Analysis of 44 different analytes in the serum of patients with relapsed or refractory LBCL treated with axi-cel showed that an increase in IL-6 or IL-1 may be associated with such toxicity. 3 However, in 2 murine models, whereas IL-6 blockade (typically achieved in clinical practice with the use of tocilizumab) prevented CRS only, only IL-1 blockade prevented both CRS and/or ICANS. 4,5 IL-1 blockade can be clinically achieved with the use of anakinra, an IL-1 receptor antagonist, currently approved by the US Food and Drug Administration for the treatment of patients with rheumatoid arthritis and neonatal-onset multisystem inflammatory disease. Anakinra is also used off label for the treatment of secondary hemophagocytic lymphohistiocytosis (HLH), a condition in the spectrum of CRS potentially associated with chimeric antigen receptor (CAR) T-cell therapy. Data regarding the clinical use of anakinra for the mitigation of axi-cel-associated toxicity have not been published.