Peripheral blasts at apheresis as a risk factor for survival after tisagenlecleucel in children and young adults

Abstract: Precursor B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignant neoplasm. Relapsed or refractory (R/R) B-ALL carries a dismal prognosis. CD19-specific chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment, yet relapse rates among responders remain high, with 40% to 50% experiencing relapse after therapy. This underscores the need for improved strategies to predict and prevent relapses after CAR T-cell therapy. This study reports the impact of peripheral blasts at the time of apheresis on outcomes in pediatric and young adult patients with R/R B-ALL treated with CD19-specific CAR T-cell therapy. A multi-institutional cohort of 162 patients from the Pediatric Real-World CAR Consortium was retrospectively analyzed. Key outcomes, such as day 28 response, event-free survival (EFS), and overall survival (OS), were evaluated based on the presence vs absence of peripheral blasts at apheresis. Although response at day 28 was comparable among peripheral blast groups in this cohort, the presence of peripheral blasts at apheresis was associated with inferior EFS (27% vs 55% at 12 months) and OS (55% vs 78% at 12 months). However, this association was confounded by disease burden at the time of infusion. In multivariable analysis, higher blast percentage at apheresis was not associated with an increased hazard of death (hazard ratio, 1.11; 95% confidence interval, 0.93-1.33; P = .25). These findings suggest that the association between peripheral blasts at apheresis and inferior survival is largely influenced by disease burden at infusion.