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

Blood. 2016 May 19;127(20):2406-10. doi: 10.1182/blood-2015-08-665547. Epub 2016 Feb 23.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT02028455.

Publication types

  • Case Reports

MeSH terms

  • Antigens, CD19 / genetics*
  • Antigens, CD19 / immunology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow / pathology
  • Chromosomes, Human, Pair 11 / genetics
  • Clone Cells
  • Combined Modality Therapy
  • Female
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Immunophenotyping
  • Immunotherapy, Adoptive*
  • Infant
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / pathology
  • Lymphocyte Depletion
  • Middle Aged
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Neoplastic Stem Cells
  • Oncogene Proteins, Fusion / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Receptors, Antigen, T-Cell / immunology*
  • Recurrence
  • Remission Induction
  • Salvage Therapy
  • T-Lymphocyte Subsets / immunology*
  • Translocation, Genetic
  • Tumor Escape*

Substances

  • Antigens, CD19
  • CD19 molecule, human
  • CD19-specific chimeric antigen receptor
  • KMT2A protein, human
  • Oncogene Proteins, Fusion
  • Receptors, Antigen, T-Cell
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase

Associated data

  • ClinicalTrials.gov/NCT02028455