Summary of published literature reporting on use of anakinra with CAR T-cell toxicities
| Author . | Study type . | Summary of study . | Anakinra use . | Dosage, frequency, route . | Response . |
|---|---|---|---|---|---|
| Lichtenstein et al18 Shah et al27 | Phase 1 trial (of CD22 CAR T cells) | 58 children and young adults treated with CD22 CAR T-cells for r/r B-ALL | 19 patients developed carHLH; 3 patients treated with anakinra alone, 5 patients treated with anakinra and steroids | 2.5-4 mg/kg/dose bid, SC | All 8 participants had improvement in carHLH. Improvement in carHLH toxicity following 1 mo of anakinra reported in 1 patient. No apparent negative impact on CAR T-cell efficacy. Specifically (restricting to a uniformly treated cohort): 17 of 19 (89.5%) patients with carHLH and 22 of 32 (68.8%) patients without carHLH achieved a CR (P = .17) Among those receiving anakinra (n = 9), 8 achieved a CR. Suboptimally treated carHLH was associated with infection risk. Unable to separate infection risk from additional immunosuppression vs underlying toxicity of CAR T cells. |
| Jatiani et al17 | Case series | 2 adult patients treated with anti-BCMA CART for MM | Anakinra used in combination with tocilizumab in 1 patient | 200 mg/dose, tid, SC | Improvement in fever and inflammatory markers following initiation of anakinra. |
| Strati et al15 | Case series | 8 adults treated with axicabtagene ciloleucel for r/r LBCL. | 8 patients treated with anakinra; 6 treated for ICANS and 2 treated for carHLH | 50-200 mg/dose, daily, SC | 4 patients treated for ICANS responded; no response in 2 patients treated for ICANS and 2 patients treated for carHLH. |
| Dreyzin et al19 | Case series | 3 pediatric patients treated with tisagenlecleucel for r/r B-ALL | 3 patients treated with anakinra, steroids, tocilizumab. Indication: ICANS, CRS, carHLH | 2-2.5 mg/kg/dose, qid, IV | All 3 patients had improvement in ICANS, CRS or HLH within 1-2 d of initiating anakinra but one of these patients needed prolonged course of anakinra for HLH with eventual improvement CAR T-cells detectable in blood at day +28 in 2/3 patients and all achieved an MRDnegative CR. None of these patients had any new infection after initiation of anakinra. |
| Hines et al20 | Case series | 27 pediatric and young adult patients treated with tisagenlecleucel or SJCAR19 | 4 carHLH patients treated with anakinra in conjunction with steroids (n= 3) and ruxolitinib (n = 1) | Not reported | Three patients demonstrated improvement following anakinra (with concurrent use of steroids). carHLH patients experienced early death and were less likely to respond to CAR T-cell therapy. |
| Oliai et al23 | Case series (abstract) | 13 adult patients treated with axicabtagene ciloleucel for r/r LBCL | 7 patients met criteria to start anakinra (any grade ICANS or grade ≥ 3 CRS in the absence of ICANS); continued until ICANS returned to grade ≤ 1 | 100 mg/dose, qid, SC | Of the 7 participants who received anakinra prior to severe ICANS, only 1 of 7 (14%) developed grade 3 ICANS. |
| Gazeau et al21 | Case series (abstract) | 26 adult patients with B-cell or plasma cell malignancies | 23 patients treated with anakinra for steroid-refractory ICANS; 2 were treated for tocilizumab-refractory CRS, 1 for both | 100-200 mg/day SC or 8 mg/kg/day SC or IV | CRS/ICANS improvement was observed in 73% of patients; higher response rates in patients receiving higher dose (8 mg/kg/day). Complete responses to CAR T-cell therapy seen in patients receiving anakinra, implying limited impact on CAR T-cell function. CR rates were high in patients receiving anakinra (53% vs 42%, P = not significant). |
| Park et al24 | Phase 2 study of anakinra (abstract) | 31 adult patients with r/r LBCL or MCL receiving commercially available CART19 | Starting on day +2 for all patients, or after 2 documented fevers prior to day 2 for prevention of ICANS and CRS | 100 mg/dose, bid, SC | Early use of anakinra may reduce the rates of severe CRS and ICANS. |
| Wehrli et al22 | Case series | 14 adult patients with steroid-refractory ICANS with or without CRS after treatment with tisagenlecleucel or axicabtagene ciloleucel | Anakinra initiated at a median of 8.5 d after CAR T-cell infusion for corticosteroids refractory ICANS | 100–200 mg/day SC | Difficult to ascertain the direct effect of anakinra on improvement in ICANS given the concomitant use of corticosteroids, but it could have possibly shortened the duration of neurological toxicities. |
| Author . | Study type . | Summary of study . | Anakinra use . | Dosage, frequency, route . | Response . |
|---|---|---|---|---|---|
| Lichtenstein et al18 Shah et al27 | Phase 1 trial (of CD22 CAR T cells) | 58 children and young adults treated with CD22 CAR T-cells for r/r B-ALL | 19 patients developed carHLH; 3 patients treated with anakinra alone, 5 patients treated with anakinra and steroids | 2.5-4 mg/kg/dose bid, SC | All 8 participants had improvement in carHLH. Improvement in carHLH toxicity following 1 mo of anakinra reported in 1 patient. No apparent negative impact on CAR T-cell efficacy. Specifically (restricting to a uniformly treated cohort): 17 of 19 (89.5%) patients with carHLH and 22 of 32 (68.8%) patients without carHLH achieved a CR (P = .17) Among those receiving anakinra (n = 9), 8 achieved a CR. Suboptimally treated carHLH was associated with infection risk. Unable to separate infection risk from additional immunosuppression vs underlying toxicity of CAR T cells. |
| Jatiani et al17 | Case series | 2 adult patients treated with anti-BCMA CART for MM | Anakinra used in combination with tocilizumab in 1 patient | 200 mg/dose, tid, SC | Improvement in fever and inflammatory markers following initiation of anakinra. |
| Strati et al15 | Case series | 8 adults treated with axicabtagene ciloleucel for r/r LBCL. | 8 patients treated with anakinra; 6 treated for ICANS and 2 treated for carHLH | 50-200 mg/dose, daily, SC | 4 patients treated for ICANS responded; no response in 2 patients treated for ICANS and 2 patients treated for carHLH. |
| Dreyzin et al19 | Case series | 3 pediatric patients treated with tisagenlecleucel for r/r B-ALL | 3 patients treated with anakinra, steroids, tocilizumab. Indication: ICANS, CRS, carHLH | 2-2.5 mg/kg/dose, qid, IV | All 3 patients had improvement in ICANS, CRS or HLH within 1-2 d of initiating anakinra but one of these patients needed prolonged course of anakinra for HLH with eventual improvement CAR T-cells detectable in blood at day +28 in 2/3 patients and all achieved an MRDnegative CR. None of these patients had any new infection after initiation of anakinra. |
| Hines et al20 | Case series | 27 pediatric and young adult patients treated with tisagenlecleucel or SJCAR19 | 4 carHLH patients treated with anakinra in conjunction with steroids (n= 3) and ruxolitinib (n = 1) | Not reported | Three patients demonstrated improvement following anakinra (with concurrent use of steroids). carHLH patients experienced early death and were less likely to respond to CAR T-cell therapy. |
| Oliai et al23 | Case series (abstract) | 13 adult patients treated with axicabtagene ciloleucel for r/r LBCL | 7 patients met criteria to start anakinra (any grade ICANS or grade ≥ 3 CRS in the absence of ICANS); continued until ICANS returned to grade ≤ 1 | 100 mg/dose, qid, SC | Of the 7 participants who received anakinra prior to severe ICANS, only 1 of 7 (14%) developed grade 3 ICANS. |
| Gazeau et al21 | Case series (abstract) | 26 adult patients with B-cell or plasma cell malignancies | 23 patients treated with anakinra for steroid-refractory ICANS; 2 were treated for tocilizumab-refractory CRS, 1 for both | 100-200 mg/day SC or 8 mg/kg/day SC or IV | CRS/ICANS improvement was observed in 73% of patients; higher response rates in patients receiving higher dose (8 mg/kg/day). Complete responses to CAR T-cell therapy seen in patients receiving anakinra, implying limited impact on CAR T-cell function. CR rates were high in patients receiving anakinra (53% vs 42%, P = not significant). |
| Park et al24 | Phase 2 study of anakinra (abstract) | 31 adult patients with r/r LBCL or MCL receiving commercially available CART19 | Starting on day +2 for all patients, or after 2 documented fevers prior to day 2 for prevention of ICANS and CRS | 100 mg/dose, bid, SC | Early use of anakinra may reduce the rates of severe CRS and ICANS. |
| Wehrli et al22 | Case series | 14 adult patients with steroid-refractory ICANS with or without CRS after treatment with tisagenlecleucel or axicabtagene ciloleucel | Anakinra initiated at a median of 8.5 d after CAR T-cell infusion for corticosteroids refractory ICANS | 100–200 mg/day SC | Difficult to ascertain the direct effect of anakinra on improvement in ICANS given the concomitant use of corticosteroids, but it could have possibly shortened the duration of neurological toxicities. |
Abbreviations: BID: Twice daily; CR, complete remission; CRS: cytokine release syndrome; d: day; HLH: hemophagocytic lymphohistiocytosis; ICANS: Immune effector cell associated neurotoxicity syndrome; IV: intravenous; LBCL, large B-cell lymphoma; MCL, mantle cell lymphoma; MM, multiple myeloma; MRD, minimal residual disease; QID: four times/day; r/r, relapsed or refractory; SC: subcutaneous; r/r: relapsed/refractory; TID: three times/day.