Multi-institutional experience with anakinra utilization in children and summary of experiences with anakinra in refractory or delayed pediatric CAR T-cell therapy–associated toxicities
| Institution . | Utilization . | Indications . | Initial dosing . | Duration of therapy . |
|---|---|---|---|---|
| Children’s National Hospital (Washington, DC) | CRS, ICANS and carHLH with CD19 CAR T-cells | Third line after steroids and tocilizumab | 2 mg/kg Q6H IV, max dose 100 mg (max daily dose of 400 mg) | Days to 2 wk, including taper over 3 d-1 wk. Taper is initiated with resolution of toxicity or CRS/ICANS ≤grade 2. Also serves as steroid or tocilizumab sparing agent and is the last medication to be weaned for CAR T-cell toxicities. See Dreyzin et al in Table 2 for specific cases |
| Seattle Children’s Hospital (Seattle, WA) | Primarily for grade 3-4 ICANS, rarely in severe CRS | ICANS: anakinra usually initiated with steroid dosing in severe ICANS CRS: anakinra may be considered following an initial dose of tocilizumab and steroids, prior to re-dosing of tocilizumab | 2 mg/kg IV, up to Q6H, max dose 100 mg (max daily dose of 400 mg). Higher doses have been used in rare circumstances | Varies, but typically remains on until resolution of toxicity for which it was initiated is ≤grade 2, or until grade of AE for which it was started is grade 2 or lower. It is typically the last agent to be weaned off. |
| Children’s Hospital of Philadelphia (Philadelphia, PA) | Severe/refractory CRS and for prolonged refractory thrombocytopenia after CD22 CAR T-cells | After nonresponse to standard tocilizumab and steroids | 2 mg/kg/day, increased up to maximum daily dose of 10 mg/kg/day (max daily dose of 400 mg), IV or SC | Varies from days to weeks. |
| Center for Cancer Research, National Institutes of Health, Clinical Center (Bethesda, MD) | CarHLH with CD22 CAR T-cells | Usually given in conjunction with steroids for patients who are more severely affected. Consider as 1st line for isolated, late onset/delayed systemic toxicities (eg, carHLH) where tocilizumab is not indicated (eg, no fevers, hypotension) | 8-10 mg/kg/day SC in cases of severe carHLH. Goal to taper down to 5-7 mg/kg/day | Varies from days to weeks. See Lichtenstein et al and Shah et al in Table 2 for specific cases |
| Medical University of South Carolina (Charleston, SC) | CRS, ICANS and carHLH with CD19 CAR T-cells | After non-response to standard tocilizumab and steroids | CRS: 4 mg/kg/dose Q12H SC then taper to 2 mg/kg/dose Q12H Alternatively, 100 mg daily (SC) for 3-4 d, then 50 mg daily SC with taper | 48-72 h for initial dosing, longer if no clinical stability/improvement, 2-3 d for taper if continuing to improve. Total duration generally 6-10 d |
| St. Jude Children’s Research Hospital (Memphis, TN) | CarHLH with CD19 CAR T-cells | First line for carHLH Often given in conjunction with tocilizumab, steroids, and/or ruxolitinib for patients who are more severely affected | 10 mg/kg/day divided Q6H SC/IV (round dose to nearest vial) | Varies from days to weeks. Begin to wean once clinical stability and/or improvement. Anakinra is the last agent to be weaned if multiple agents are being used. See Hines et al in Table 2 for specific cases |
| Institution . | Utilization . | Indications . | Initial dosing . | Duration of therapy . |
|---|---|---|---|---|
| Children’s National Hospital (Washington, DC) | CRS, ICANS and carHLH with CD19 CAR T-cells | Third line after steroids and tocilizumab | 2 mg/kg Q6H IV, max dose 100 mg (max daily dose of 400 mg) | Days to 2 wk, including taper over 3 d-1 wk. Taper is initiated with resolution of toxicity or CRS/ICANS ≤grade 2. Also serves as steroid or tocilizumab sparing agent and is the last medication to be weaned for CAR T-cell toxicities. See Dreyzin et al in Table 2 for specific cases |
| Seattle Children’s Hospital (Seattle, WA) | Primarily for grade 3-4 ICANS, rarely in severe CRS | ICANS: anakinra usually initiated with steroid dosing in severe ICANS CRS: anakinra may be considered following an initial dose of tocilizumab and steroids, prior to re-dosing of tocilizumab | 2 mg/kg IV, up to Q6H, max dose 100 mg (max daily dose of 400 mg). Higher doses have been used in rare circumstances | Varies, but typically remains on until resolution of toxicity for which it was initiated is ≤grade 2, or until grade of AE for which it was started is grade 2 or lower. It is typically the last agent to be weaned off. |
| Children’s Hospital of Philadelphia (Philadelphia, PA) | Severe/refractory CRS and for prolonged refractory thrombocytopenia after CD22 CAR T-cells | After nonresponse to standard tocilizumab and steroids | 2 mg/kg/day, increased up to maximum daily dose of 10 mg/kg/day (max daily dose of 400 mg), IV or SC | Varies from days to weeks. |
| Center for Cancer Research, National Institutes of Health, Clinical Center (Bethesda, MD) | CarHLH with CD22 CAR T-cells | Usually given in conjunction with steroids for patients who are more severely affected. Consider as 1st line for isolated, late onset/delayed systemic toxicities (eg, carHLH) where tocilizumab is not indicated (eg, no fevers, hypotension) | 8-10 mg/kg/day SC in cases of severe carHLH. Goal to taper down to 5-7 mg/kg/day | Varies from days to weeks. See Lichtenstein et al and Shah et al in Table 2 for specific cases |
| Medical University of South Carolina (Charleston, SC) | CRS, ICANS and carHLH with CD19 CAR T-cells | After non-response to standard tocilizumab and steroids | CRS: 4 mg/kg/dose Q12H SC then taper to 2 mg/kg/dose Q12H Alternatively, 100 mg daily (SC) for 3-4 d, then 50 mg daily SC with taper | 48-72 h for initial dosing, longer if no clinical stability/improvement, 2-3 d for taper if continuing to improve. Total duration generally 6-10 d |
| St. Jude Children’s Research Hospital (Memphis, TN) | CarHLH with CD19 CAR T-cells | First line for carHLH Often given in conjunction with tocilizumab, steroids, and/or ruxolitinib for patients who are more severely affected | 10 mg/kg/day divided Q6H SC/IV (round dose to nearest vial) | Varies from days to weeks. Begin to wean once clinical stability and/or improvement. Anakinra is the last agent to be weaned if multiple agents are being used. See Hines et al in Table 2 for specific cases |
Abbreviations: BID, twice daily; CRS, cytokine release syndrome; d, day; HLH, hemophagocytic lymphohistiocytosis; ICANS, immune effector cell associated neurotoxicity syndrome; IV, intravenous; MRD, minimal residual disease; QID, four times/day; r/r, relapsed/refractory; SC, subcutaneous; TID, three times/day.