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

Fiche publication


Date publication

août 2024

Journal

Journal of hematology & oncology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr CASASNOVAS Olivier, Pr RUBIO Marie Thérèse


Tous les auteurs :
Sesques P, Kirkwood AA, Kwon M, Rejeski K, Jain MD, Di Blasi R, Brisou G, Gros FX, le Bras F, Bories P, Choquet S, Rubio MT, Iacoboni G, O'Reilly M, Casasnovas RO, Bay JO, Mohty M, Joris M, Abraham J, Castilla Llorente C, Loschi M, Carras S, Chauchet A, La Rochelle LD, Hermine O, Guidez S, Cony-Makhoul P, Fogarty P, Le Gouill S, Morschhauser F, Gastinne T, Cartron G, Subklewe M, Locke FL, Sanderson R, Barba P, Houot R, Bachy E

Résumé

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.

Mots clés

Humans, Immunotherapy, Adoptive, adverse effects, Male, Female, Middle Aged, Antigens, CD19, immunology, Prognosis, Lymphoma, Large B-Cell, Diffuse, therapy, Cytokine Release Syndrome, etiology, Aged, Adult, Neurotoxicity Syndromes, etiology, Biological Products, therapeutic use, France, Aged, 80 and over, Receptors, Antigen, T-Cell

Référence

J Hematol Oncol. 2024 08 6;17(1):61