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

Author:

Sesques Pierre,Kirkwood Amy A.,Kwon Mi,Rejeski Kai,Jain Michael D.,Di Blasi Roberta,Brisou Gabriel,Gros François-Xavier,le Bras Fabien,Bories Pierre,Choquet Sylvain,Rubio Marie-Thérèse,Iacoboni Gloria,O’Reilly Maeve,Casasnovas René-Olivier,Bay Jacques-Olivier,Mohty Mohamad,Joris Magalie,Abraham Julie,Castilla Llorente Cristina,Loschi Mickael,Carras Sylvain,Chauchet Adrien,La Rochelle Laurianne Drieu,Hermine Olivier,Guidez Stéphanie,Cony-Makhoul Pascale,Fogarty Patrick,Le Gouill Steven,Morschhauser Franck,Gastinne Thomas,Cartron Guillaume,Subklewe Marion,Locke Frederick L.,Sanderson Robin,Barba Pere,Houot Roch,Bachy Emmanuel

Abstract

AbstractAutologous 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.

Publisher

Springer Science and Business Media LLC

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