Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Aug 6;17(1):61.
doi: 10.1186/s13045-024-01579-w.

Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma

Pierre Sesques  1 , Amy A Kirkwood  2 , Mi Kwon  3 , Kai Rejeski  4 , Michael D Jain  5 , Roberta Di Blasi  6 , Gabriel Brisou  7 , François-Xavier Gros  8 , Fabien le Bras  9 , Pierre Bories  10 , Sylvain Choquet  11 , Marie-Thérèse Rubio  12 , Gloria Iacoboni  13   14 , Maeve O'Reilly  15 , René-Olivier Casasnovas  16 , Jacques-Olivier Bay  17 , Mohamad Mohty  18 , Magalie Joris  19 , Julie Abraham  20 , Cristina Castilla Llorente  21 , Mickael Loschi  22 , Sylvain Carras  23 , Adrien Chauchet  24 , Laurianne Drieu La Rochelle  25 , Olivier Hermine  26 , Stéphanie Guidez  27 , Pascale Cony-Makhoul  28 , Patrick Fogarty  29 , Steven Le Gouill  30 , Franck Morschhauser  31   32 , Thomas Gastinne  33 , Guillaume Cartron  34 , Marion Subklewe  4 , Frederick L Locke  5 , Robin Sanderson  35 , Pere Barba  13   14 , Roch Houot  36 , Emmanuel Bachy  37   38
Affiliations

Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma

Pierre Sesques et al. J Hematol Oncol. .

Abstract

Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count < 150 G/L, a C-reactive protein (CRP) level > 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets (< 150 G/L), use of axi-cel and no bridging therapy or SD/PD after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.

Trial registration: ClinicalTrials.gov NCT04328298.

PubMed Disclaimer

Conflict of interest statement

P.S: Honoraria, Advisory/Consultancy from Janssen, Roche, BMS, Chugai; Novartis and Kite/Gilead; A.K: Honoraria from Kite/Gilead; M.K: no conflict to declare; K.R. Kite/Gilead: Research Funding and travel support; Novartis: Honoraria; BMS/Celgene: Consultancy, Honoraria; Pierre-Fabre: travel support; MDJ: Consult/advisor for Kite/Gilead and Myeloid Therapeutics; research funding from Kite/Gilead, Incyte, and Loxo@Lilly; R.DB: Honoraria, travel support, and membership of advisory boards from Novartis,Kite/Gilead, Janssen, Pfizer, Celgene; G.B: Honoraria and travel fees from: Kite/Gilead, BMS, Incyte, Novartis; FX.G: Honoraria: Kite/Gilead, BMS, Milteny, Novartis.Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria; F.LB: Takeda: Honoraria, Research Funding; Kite Gilead: Honoraria; Novartis: Honoraria; Celgene BMS: Research Funding; P.B. declares having received honoraria from Allogene, Amgen, BMS, Kit/Gilead, Incyte, Jazz Pharmaceuticals, Miltenyi Biomedicine, Nektar Novartis and Pierre Fabre; MTR: No COIs; G.I:Honoraria and travel support: Novartis, Kite/Gilead, Bristol-Myers Squibb, Abbvie, Autolus, Sandoz, Janssen, Miltenyi, AstraZeneca; MOR: no conflict to declare; ROC Honoraria for consultancy and advisory board:Roche, Takeda, BMS,MSD, Gilead/Kite, Janssen, ADC Therapeutics, Incyte; Research funding: Roche,Gilead, Takeda; JO.B: no conflict to declare; M.M.: No COIs; M.J: no conflict to declare; J.A: No COIs; CCLl: Honoraria from Gilead/Kite, Nektar Therapeutics; M.L: no conflict to declare; S.C: Kite/gilead: Consultancy and Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees and Research Funding; Abbvie; Other: Travelfees; Beigene: Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Membership on an entity's Board of Directors or advisory committees, Other: travel fees and Research Funding; A.C.: No COIs; L. DDLR: No COIs; O.H: No COIs; S.G: No COIs; P.CM: COIs; P.F: No COIs; S.LG: Honoraria, travel support, and membership of advisory boards from Novartis, Kite/Gilead, Janssen; F.M: Advisory boards pour Gilead, Novartis, BMS, épizyme, miltenyi,Abbvie, genmab, Roche, AstraZeneca; Consultancy: gilead, roche; Scientific lectures:Roche, Chugai; T.G: honoraria from Gilead/kite, Novartis, Takeda; G.C: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria; M.S. receives industry research support from Amgen, BMS/Celgene, Gilead, Janssen, Miltenyi Biotec, Novartis, Roche, Seattle Genetics and Takeda and serves as a consultant/advisor to AvenCell, CDR-Life, Ichnos Sciences, Incyte Biosciences, Janssen, Miltenyi Biotec, Molecular Partners, Novartis, Pfizer and Takeda. She serves on the speakers’ bureau at Amgen, AstraZeneca, BMS/Celgene, Gilead, GSK, Janssen, Novartis, Pfizer, Roche and Takeda; P.B. declares having received honoraria from Novartis, Kite Gilead, BMS Celgene and Abbvie; F.L.L: has a scientific advisory role with Kite, a Gilead Company, Novartis, Celgene/Bristol-Myers Squibb, GammaDelta Therapeutics, Wugen, Amgen, Calibr, and Allogene; is a consultant with grant options for Cellular Biomedicine Group, Inc.; and receives research support from Kite, a Gilead Company, Novartis, and Allogene; and reports that his institution holds unlicensed patents in his name in the field of cellular immunotherapy; R.S: No COIs; R.H: Honoraria from Bristol-Myers Squibb, Celgene, Gilead Sciences, Incyte, Janssen, Kite, MSD, Novartis and Roche; EB: Honoraria from Kite, a Gilead Company, Bristol Myers Squibb, Novartis, Pfizer, Incyte, ADC Therapeutics; personal fees from Kite, a Gilead Company, Bristol Myers Squibb, Novartis, Pfizer; research funding paid to institution from Amgen, BMS.; P.S: Honoraria, Advisory/Consultancy from Janssen, Roche, BMS, Chugai; Novartis and Kite/Gilead A.K: Honoraria from Kite/Gilead M.K: no conflict to declare K.R. Kite/Gilead: Research Funding and travel support; Novartis: Honoraria; BMS/Celgene: Consultancy, Honoraria; Pierre-Fabre: travel support MDJ: Consult/advisor for Kite/Gilead and Myeloid Therapeutics; research funding from Kite/Gilead, Incyte, and Loxo@Lilly. R.DB: Honoraria, travel support, and membership of advisory boards from Novartis,Kite/Gilead, Janssen, Pfizer, Celgene. G.B: Honoraria and travel fees from: Kite/Gilead, BMS, Incyte, Novartis FX.G: Honoraria: Kite/Gilead, BMS, Milteny, Novartis.Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria. F.LB: Takeda: Honoraria, Research Funding; Kite Gilead: Honoraria; Novartis: Honoraria; Celgene BMS: Research Funding. P.B. declares having received honoraria from Allogene, Amgen, BMS, Kit/Gilead, Incyte, Jazz Pharmaceuticals, Miltenyi Biomedicine, Nektar Novartis and Pierre Fabre. MTR: No COIs. G.I:Honoraria and travel support: Novartis, Kite/Gilead, Bristol-Myers Squibb, Abbvie, Autolus, Sandoz, Janssen, Miltenyi, AstraZeneca MOR: no conflict to declare ROC Honoraria for consultancy and advisory board:Roche, Takeda, BMS,MSD, Gilead/Kite, Janssen, ADC Therapeutics, Incyte; Research funding: Roche,Gilead, Takeda JO.B: no conflict to declare M.M.: No COIs. M.J: no conflict to declare J.A: No COIs. CCLl: Honoraria from Gilead/Kite, Nektar Therapeutics M.L: no conflict to declare S.C: Kite/gilead: Consultancy and Membership on an entity's Board of Directors or advisory committees Astrazeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees and Research Funding; Abbvie; Other: Travelfees; Beigene: Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Membership on an entity's Board of Directors or advisory committees, Other: travel fees and Research Funding A.C.: No COIs. L. DDLR: No COIs. O.H: No COIs. S.G: No COIs. P.CM: COIs. P.F: No COIs. S.LG: Honoraria, travel support, and membership of advisory boards from Novartis, Kite/Gilead, Janssen F.M: Advisory boards pour Gilead, Novartis, BMS, épizyme, miltenyi,Abbvie, genmab, Roche, AstraZeneca; Consultancy: gilead, roche; Scientific lectures:Roche, Chugai T.G: honoraria from Gilead/kite, Novartis, Takeda G.C: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. M.S. receives industry research support from Amgen, BMS/Celgene, Gilead, Janssen, Miltenyi Biotec, Novartis, Roche, Seattle Genetics and Takeda and serves as a consultant/advisor to AvenCell, CDR-Life, Ichnos Sciences, Incyte Biosciences, Janssen, Miltenyi Biotec, Molecular Partners, Novartis, Pfizer and Takeda. She serves on the speakers’ bureau at Amgen, AstraZeneca, BMS/Celgene, Gilead, GSK, Janssen, Novartis, Pfizer, Roche and Takeda. P.B. declares having received honoraria from Novartis, Kite Gilead, BMS Celgene and Abbvie F.L.L: has a scientific advisory role with Kite, a Gilead Company, Novartis, Celgene/Bristol-Myers Squibb, GammaDelta Therapeutics, Wugen, Amgen, Calibr, and Allogene; is a consultant with grant options for Cellular Biomedicine Group, Inc.; and receives research support from Kite, a Gilead Company, Novartis, and Allogene; and reports that his institution holds unlicensed patents in his name in the field of cellular immunotherapy. R.S: No COIs. R.H: Honoraria from Bristol-Myers Squibb, Celgene, Gilead Sciences, Incyte, Janssen, Kite, MSD, Novartis and Roche EB: Honoraria from Kite, a Gilead Company, Bristol Myers Squibb, Novartis, Pfizer, Incyte, ADC Therapeutics; personal fees from Kite, a Gilead Company, Bristol Myers Squibb, Novartis, Pfizer; research funding paid to institution from Amgen, BMS.

Figures

Fig. 1
Fig. 1
Day 28 landmark survival analysis according to toxicity grade for patients treated with tisa-cel. A PFS according to CRS grade. B OS according to CRS grade. C PFS according to ICANS grade. D OS according to ICANS grade
Fig. 2
Fig. 2
Day 28 landmark survival analysis according to toxicity grade for patients treated with axi-cel. A PFS according to CRS grade. B OS according to CRS grade. C PFS according to ICANS grade. D OS according to ICANS grade
See this image and copyright information in PMC

References

    1. Schuster SJ, Tam CS, Borchmann P, et al. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021;22(10):1403–15. - PubMed
    1. Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial. Lancet Oncol. 2019;20(1):31–42. - PMC - PubMed
    1. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396(10254):839–52. - PubMed
    1. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640–54. - PubMed
    1. Bishop MR, Dickinson M, Purtill D, et al. Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma. N Engl J Med. 2022;386(7):629–39. - PubMed

Associated data

LinkOut - more resources