Clinical efficacy of anakinra to mitigate CAR T-cell therapy–associated toxicity in large B-cell lymphoma
Paolo Strati, Sairah Ahmed, Partow Kebriaei, Loretta J. Nastoupil, Catherine M. Claussen, Grace Watson, Sandra B. Horowitz, Anne Rain Brown, Bryan Do, Maria Alma Rodriguez, Ranjit Nair, Elizabeth J. Shpall, Michael R. Green, Sattva S. Neelapu, Jason R. Westin
Abstract
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.