Outcomes of CD19-directed CAR T-cell therapy in R/R extramedullary B‑ALL

Results from a multicenter, retrospective analysis, evaluating clinical outcomes in children and young adults with relapsed/refractory (R/R) B‑cell acute lymphoblastic leukemia (B‑ALL) treated with CD19-directed chimeric antigen receptor (CAR) T‑cell therapy (N = 308), with a particular focus on patients with extramedullary disease (EMD), were published in Blood Advances by Rankin et al. Study participants were stratified into three cohorts based on disease site at infusion: isolated bone marrow (BM) disease (n = 251), active non-central nervous system (CNS) EMD (n = 21), and active CNS disease (n = 36). Patients were further stratified into high BM disease burden (≥5% blasts) and low BM disease burden (<5% blasts). Response was assessed at Day 21–28 post-infusion. 

Key data: Among 208 patients with detectable BM disease at the time of infusion, measurable residual disease (MRD) negativity was observed in 75.0%, 84.0%, and 93.4% of patients in the EMD, CNS, and isolated BM cohorts, respectively (p = 0.019). Among 17 evaluable patients in the EMD cohort, 82.4% achieved complete response (CR) of their EMD, while 17.6% had progressive disease (PD). At 24 months, overall survival (OS) was 66.7%, 57.0%, and 71.5% for the EMD, CNS, and isolated BM cohorts, respectively (p = 0.032). Within the EMD cohort, 24-month OS was 100% with low BM disease burden (<5% blasts) vs 41.7% with high BM disease burden (≥5% blasts; p = 0.005); within the CNS cohort, 24‑month OS was 92.3% vs 33.3%, respectively (p = 0.001).  

Key learning: CD19-directed CAR T‑cell therapy achieved meaningful clinical responses in children and young adults with R/R B‑ALL and active EMD or CNS disease, particularly in the setting of low BM disease burden.