RT Journal Article
SR Electronic
T1 Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e003847
DO 10.1136/jitc-2021-003847
VO 10
IS 1
A1 Marc Wehrli
A1 Kathleen Gallagher
A1 Yi-Bin Chen
A1 Mark B Leick
A1 Steven L McAfee
A1 Areej R El-Jawahri
A1 Zachariah DeFilipp
A1 Nora Horick
A1 Paul O'Donnell
A1 Thomas Spitzer
A1 Bimal Dey
A1 Daniella Cook
A1 Michael Trailor
A1 Kevin Lindell
A1 Marcela V Maus
A1 Matthew J Frigault
YR 2022
UL http://jitc.bmj.com/content/10/1/e003847.abstract
AB 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.Data are available upon reasonable request.