PROGNOSTIC SCORING SYSTEMS FOR SEVERE CRS AND ICANS AFTER AUTOLOGOUS ANTI‐CD19 CAR T CELLS IN LARGE B‐CELL LYMPHOMA: A DESCAR‐T REGISTRY STUDY FORM THE LYSA (2023)

Background: Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are common immune-related toxicities associated with chimeric antigen receptor (CAR)–T-cell therapy. Their clinical manifestations can be severe and potentially life threatening. Aims: Here, we report on specific acute toxicities of CAR-T in a large real-world evidence population treated with axi-cel or tisa-cel for refractory/relapse aggressive B-cell lymphoma (R/R ABCL) and we propose two validated prognostic scoring systems to refine the identification of patients at high risk of severe CRS or ICANS before any CAR-T cell infusion. Methods: We conducted a study in a large cohort of R/R ABCL patients (pts) treated with commercial products as third-line therapy. All data were collected through the French DESCAR-T registry. CRS/ICANS were graded according to the ASTCT grading scale. For prognosis scoring system computation, the data set was split into a training set (N = 555) to derive optimal predictive models, and the remaining 40% of records were used as a first validation set to test their validity (N = 370). Boostrap analyses were used to identify robust prognostic parameters and models in the training set. Results: Toxicity was analyzed for 925 pts receiving CAR-T cells in third-line setting, with a median follow-up of 12.7 months (range: 0.2–39). CRS of any grade occurred in 778 pts (84.1%) including 74 (8.0%) with grade 3 or higher. ICANS of any grade occurred in 375 pts (40.5%) including 110 (11.9%) with grade ≥3. Based on the parameters selected by multivariate analyses, two independent prognostic scoring systems (PSS) were derived for grade ≥3 CRS and grade ≥3 ICANS based on weighted coefficients and termed CRS-PSS (4-point scale) and ICANS-PSS (5-point scale) respectively (Table 1). Each score was subsequently divided into 2 classes for convenient routine use with an optimal cut-off set at 2. For severe CRS, the incidence was 6.2% in the low-risk category (CRS-PSS ≤2) compared with 20.7% in the high-risk category (CRS-PSS >2, p < 0.0001). For severe ICANS, the incidence was 2.6% in the low-risk category (ICANS-PSS ≤2) compared with 18.3% in the high-risk category (ICANS-PSS >2, p < 0.0001). The statistical prognostic significance of both CRS-PSS and ICANS-PSS were confirmed in the DESCAR-T validation cohort (p = 0.0184 and p < 0.0001, respectively). Performances of CRS-PSS and ICANS-PSS were compared with those of EASIX, modified-EASIX and simplified-EASIX and were consistently better both in the training and the validation cohorts (Table 2). Further external validation is ongoing and will be presented at the meeting. Conclusion: In this large study, we propose two pre-infusion validated and easy-to-compute scoring systems that allow for the identification of patients at higher risk of grade ≥3 CRS or ICANS for potential tailored medical care. Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies Conflicts of interests pertinent to the abstract P. Sesques Honoraria: KITE/GILEAD; BMS; CHUGAI Educational grants: KITE/GILEAD; JANSSEN R. Di blasi Honoraria: Janssen, Pfizer, Bristol Myers Squibb, Kite/Gilead and Novartis. S. Legouill Honoraria: Janssen-Cilag, Kite/Gilead and Novartis G. Cartron Honoraria: Roche, Bristol Myers Squibb, Onwards Therapeutics, MedxCell, EmerCell, MabQ, Sanofi, Abbvie, Takeda, Roche, Janssen, Roche, Novartis and Myltenyi D. Beauvais Honoraria: Kite/Gilead F. Gros Honoraria: Bristol Myers Squibb, Novartis and Kite/Gilead P. Bories Honoraria: Bristol Myers Squibb, Kite/Gilead, Novartis and Abbvie M. Rubio Honoraria: Novartis and Kite/Gilead. R. Casasnovas Honoraria: Roche, Takeda, Bristol Myers Squibb, Merck, Kite/ Gilead, Abbvie and ADC Therapeutics Research funding: Roche, Takeda and Kite/Gilead M. Mohty Honoraria: Adaptive Biotechnologies, Amgen, Bristol Myers Squibb, Janssen, Takeda, Novartis and Sanofi Research funding: Bristol Myers Squibb, Janssen and Sanofi J. Abraham Honoraria: Roche and Janssen-Cilag C. Castilla Llorente Honoraria: Kite/Gilead; M. Loschi Honoraria: Pfizer, Novartis, Gilead and Bristol Myers Squibb S. Carras Honoraria: Abbvie, AstraZeneca, Novartis, Janssen, Takeda, Atara, Pierre Fabre, Kite/Gilead and Viatris O. Hermine Consultant or advisory role: AB Science and Inatherys Research funding: Myers Squibb and Alexion S. Guidez Honoraria: Kite/Gilead, Incyte, Takeda and Janssen T. Gastinne Honoraria: Kite/Gilead, Pfizer and Takeda J. Tudesq Honoraria: Bristol Myers Squibb and Kite/Gilead F. Morschhauser Consultant or advisory role: Roche Honoraria: Genmab, Novartis, Kite/Gilead, Bristol Myers Squibb, AstraZeneca, Epizyme, Roche, Abbvie, Chugaï, Janssen, Incyte, Kymera, Miltenyi R. Houot Honoraria: Bristol Myers Squibb, Kite/Gilead, Incyte, Janssen, Merck Sharp & Dohme, Takeda, Novartis and Roche C. Thieblemont Honoraria: Novartis, Bristol Myers Squibb, Bayer, Abbvie, Gilead Sciences, Roche, Janssen, Kite, Incyte and Amgen E. Bachy Honoraria: Novartis, Kite/Gilead, Roche, Takeda and Incyte Research funding: Amgen Educational grants: Roche and Incyte