Although CD19-directed CAR T cells can initially induce remission in 70-90% of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), post-CAR relapses are frequent. These relapses are driven by insufficient persistence of CAR T cells, allowing for antigen-positive B-ALL re-emergence and loss of the targeted epitope either in isolation or as part of lineage-switching.