S113: IMPACT OF IKZF1 DELETION IN RELAPSED AND/OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH CD19-CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY

Background: Although CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) has emerged as one of the promising therapeutic approaches to relapsed and/or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), more than half of recipients will ultimately experience disease progression. Mounting evidence shows that resistance to CAR-T therapy influenced by the factors not only related to effector cells, but target cells. Previous studies have shown the poor outcome conferred by IKZF1 deletions, but have not been explored in the context of CAR T-cell therapy. Therefore, it is necessary to explore the impact of IKZF1 deletion on the prognostic value of patients receiving CAR-T therapy. Aims: We determined to assess the prognostic effect of IKZF1 deletion to CAR-T therapy, explore the mechanism of resistance, and develop a potential therapeutic strategy for these patients. Methods: Here we enrolled two cohorts to analyze the impact of IKZF1 deletion. The first cohort included 129 patients receiving CAR-T therapy from three centers. After that, a IKZF1 deletion cohort of 113 patients was establish to analyze whether CAR T therapy can overcome genetic adverse features, IKZF1 deletion, to induce remission. Results: Within the CAR-T cohort, the inferior EFS of enrolled patients was observed in IKZF1 deletion group (P=0.041, Fig.A). In a multivariable Cox regression model adjusting for factors contributing to event-free survival, including Ph status, immunophenotype, and chromosome karyotype, IKZF1 deletion remained independently associated with inferior event-free survival (P=0.025, Fig.B). In the cohort of patients with IKZF1 deletion, EFS rates of CAR-T group were comparable with the no-CAR-T group (Fig.C). CAR-T therapy cannot abrogate the dismal survival of patients with IKZF1 deletion in the multivariable regression models (P=0.157, Fig.D). Summary/Conclusion: IKZF1 deletion is a potent tumor-intrinsic biomarker that can inform risk stratification and clinical trial design in patients with B-ALL treated with CD19-CAR-T. Further mechanisms are needed to explore how tumor intrinsic phenotype promote resistance to the antitumor immune response, and could represent targets to potentiate the efficacy of CAR-T therapy.Keywords: CAR-T, Adult, Acute lymphoblastic leukemia