Single-center experience using anakinra for steroid-refractory immune effector cell-Associated neurotoxicity syndrome (ICANS)

• Main Authors: Chen, Y.-B (Author), Cook, D. (Author), Defilipp, Z. (Author), Dey, B. (Author), El-Jawahri, A.R (Author), Frigault, M.J (Author), Gallagher, K. (Author), Horick, N. (Author), Leick, M.B (Author), Lindell, K. (Author), Maus, M.V (Author), McAfee, S.L (Author), O'Donnell, P. (Author), Spitzer, T. (Author), Trailor, M. (Author), Wehrli, M. (Author)
• Format: Article
• Language: English
• Published: BMJ Publishing Group 2022
• Subjects: adult; Adult; aged; Aged; anakinra; Article; atovaquone; autologous stem cell transplantation; axicabtagene ciloleucel; biological marker; blood sampling; Burkitt lymphoma; C reactive protein; CD19 antigen; central nervous system; chimeric antigen receptor T-cell immunotherapy; chimeric antigen receptors; clinical article; combination; corticosteroid; cyclophosphamide; cytokine release syndrome; cytokines; dasatinib; dexamethasone; diffuse large B cell lymphoma; drug efficacy; drug therapy; effector cell; famciclovir; febrile neutropenia; female; Female; ferritin; fever; fluconazole; follicular lymphoma; gamma interferon inducible protein 10; granulocyte macrophage colony stimulating factor; hematologic malignancy; human; Humans; inflammation; interleukin 1; Interleukin 1 Receptor Antagonist Protein; interleukin 1 receptor blocking agent; interleukin 15; interleukin 18; interleukin 1alpha; interleukin 1beta; interleukin 2; interleukin 2 receptor alpha; interleukin 6; interleukin 6 receptor; interleukin 6 receptor alpha; interleukin 7; lactate dehydrogenase; lactate dehydrogenase blood level; lymphoblastoma; macrophage inflammatory protein 1alpha; macrophage inflammatory protein 1beta; male; Male; mantle cell lymphoma; middle aged; Middle Aged; monocyte chemotactic protein 1; multiplex polymerase chain reaction; Neurotoxicity Syndromes; neutropenia; neutrophil count; pathogenesis; platelet count; prophylaxis; Receptors, Chimeric Antigen; retrospective study; ruxolitinib; siltuximab; steroid; thrombocytopenia; tisagenlecleucel T; tocilizumab; toxicity and intoxication; tumor necrosis factor
• Online Access: View Fulltext in Publisher

 In addition to remarkable antitumor activity, chimeric antigen receptor (CAR) T-cell therapy is associated with acute toxicities such as cytokine release syndrome (CRS) and immune effector cell-Associated neurotoxicity syndrome (ICANS). Current treatment guidelines for CRS and ICANS include use of tocilizumab, a monoclonal antibody that blocks the interleukin (IL)-6 receptor, and corticosteroids. In patients with refractory CRS, use of several other agents as third-line therapy (including siltuximab, ruxolitinib, anakinra, dasatinib, and cyclophosphamide) has been reported on an anecdotal basis. At our institution, anakinra has become the standard treatment for the management of steroid-refractory ICANS with or without CRS, based on recent animal data demonstrating the role of IL-1 in the pathogenesis of ICANS/CRS. Here, we retrospectively analyzed clinical and laboratory parameters, including serum cytokines, in 14 patients at our center treated with anakinra for steroid-refractory ICANS with or without CRS after standard treatment with tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) CD19-Targeting CAR T. We observed statistically significant and rapid reductions in fever, inflammatory cytokines, and biomarkers associated with ICANS/CRS after anakinra treatment. With three daily subcutaneous doses, anakinra did not have a clear, clinically dramatic effect on neurotoxicity, and its use did not result in rapid tapering of corticosteroids; although neutropenia and thrombocytopenia were common at the time of anakinra dosing, there were no clear delays in hematopoietic recovery or infections that were directly attributable to anakinra. Anakinra may be useful adjunct to steroids and tocilizumab in the management of CRS and/or steroid-refractory ICANs resulting from CAR T-cell therapies, but prospective studies are needed to determine its efficacy in these settings. ©