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Chimeric antigen receptor T cell (CAR-T) therapy is used primarily to treat relapsed ALL. The most serious complications of CAR-T therapy are cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). This document outlines the treatment strategies for CRS and ICANS.
CRS can also occur in the context of haplo-identical BMT (unmatched related T-cell replete hematopoietic stem cell transplant using post-transplant cyclophosphamide) and the use of blinatumomab (Blincyto – a monoclonal antibody targeting CD-19 on B-cells) for high risk ALL.
Also immunotherapy using tumor-selective anti-disialoganglioside (anti-GD2) monoclonal antibodies for treatment of high risk neuroblastoma (dinutuximab + GM-CSF) can cause CRS. This therapy causes severe pain that is treated with combination IV hydromorphone and dexmedetomidine that can aggravate any hypotension.
Management of CRS in the context of these other oncological therapies is similar to the management of CRS after CAR-T therapy, though the thresholds for PICU admission, tocilizumab and steroids may vary.
Most Recent References
Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection. Hall EM, Yin DE, Goyal RK, Ahmed AA, Mitchell GS, St Peter SD, Flatt TG, Ahmed IA, Li W, Hendrickson RJ, August KJ, Myers GD.J Immunother Cancer. 2021 Jan;9(1):e001225.
Impact of cytokine release syndrome on cardiac function following CD19 CAR-T cell therapy in children and young adults with hematological malignancies. Shalabi H, Sachdev V, Kulshreshtha A, Cohen JW, Yates B, Rosing DR, Sidenko S, Delbrook C, Mackall C, Wiley B, Lee DW, Shah NN.J Immunother Cancer. 2020 Sep;8(2):e001159.
Diagnostic biomarkers to differentiate sepsis from cytokine release syndrome in critically ill children. Diorio C, Shaw PA, Pequignot E, Orlenko A, Chen F, Aplenc R, Barrett DM, Bassiri H, Behrens E, DiNofia AM, Gonzalez V, Koterba N, Levine BL, Maude SL, Meyer NJ, Moore JH, Paessler M, Porter DL, Bush JL, Siegel DL, Davis MM, Zhang D, June CH, Grupp SA, Melenhorst JJ, Lacey SF, Weiss SL, Teachey DT. Blood Adv. 2020 Oct 27;4(20):5174-5183.