Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy

Administration of lymphodepletion chemotherapy followed by CD19-specific chimeric antigen receptor (CAR)–modified T cells is a remarkably effective approach to treating patients with relapsed and refractory CD19+ B-cell malignancies. We treated 7 patients with B-cell acute lymphoblastic leukemia (B-ALL) harboring rearrangement of the mixed lineage leukemia (MLL) gene with CD19 CAR-T cells. All patients achieved complete remission (CR) in the bone marrow by flow cytometry after CD19 CAR-T-cell therapy; however, within 1 month of CAR-T-cell infusion, 2 of the patients developed acute myeloid leukemia (AML) that was clonally related to their B-ALL, a novel mechanism of CD19-negative immune escape. These reports have implications for the management of patients with relapsed and refractory MLL-B-ALL who receive CD19 CAR-T-cell therapy. •CD19-targeted CAR-T-cell therapy of patients with MLL-rearranged B-ALL effectively induced marrow remission of B-ALL.•Patients with MLL-rearranged B-ALL who attain CR after CD19 CAR-T-cell therapy may be at risk for relapse with clonally related AML.