Allogeneic CD19-targeted CAR-T therapy (BRL-301) for relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

e14518 Background: Despite advances in treatment, outcomes for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) remain poor, with conventional chemotherapy achieving complete remission in only 18–45% of patients. Allogeneic CAR-T cells offer an "off-the-shelf" alternative but require genome editing to mitigate host rejection and graft-versus-host disease (GvHD). This study evaluates the safety and efficacy of BRL-301, a healthy donor-derived, multiplex genome-edited allogeneic CD19-targeted CAR-T product, in patients with r/r B-ALL. Methods: In this investigator-initiated trial (NCT05381181), patients with r/r B-ALL received lymphodepletion with etoposide, cyclophosphamide, and fludarabine followed by BRL-301 infusion. Safety and response assessments were conducted per protocol. Results: Five patients (median age 16 years, range 10–45) received BRL-301. All patients achieved an objective response, with a 100% complete response rate. Robust CAR-T expansion was observed in all subjects, peaking between days 7–18 post-infusion. Grade 3/4 adverse events included cytopenias attributable to lymphodepletion. All patients experienced mild (grade 1/2) cytokine release syndrome; 4 patients received tocilizumab and steroids. No immune effector cell-associated neurotoxicity syndrome (ICANS) or GvHD was observed. Conclusions: BRL-301 demonstrated promising efficacy and a manageable safety profile in patients with r/r B-ALL, with no evidence of GvHD or severe neurotoxicity. These results support further development of allogeneic CAR-T therapy as a viable treatment option for r/r B-ALL. Clinical trial information: NCT05381181 .