Outcome of patients with relapsed/refractory acute lymphoblastic leukemia after blinatumomab failure: No change in the level of CD19 expression

Am J Hematol. 2018 Mar;93(3):371-374. doi: 10.1002/ajh.24987. Epub 2017 Dec 23.

Abstract

Blinatumomab, a bi-specific T-cell engaging CD3-CD19 antibody construct, has shown significant activity in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). Despite this improvement, most patients relapse. Here, we describe the outcome of 68 patients with R/R ALL after failure of blinatumomab therapy: 38 (56%) blinatumomab refractory; 30 (44%) relapsing after initial response. After a median follow-up of 49 months, 9 (13%) patients remained alive. The median overall survival after blinatumomab failure was 5.2 months. At the time of failure, among 61 patients evaluated for immunophenotype, 56 (92%) had CD19-positive blasts; only five (8%) had ALL recurrence with CD19-negative disease. Two patients progressed with lower CD19 expression. In summary, the outcome of patients with R/R ALL after blinatumomab failure is poor and treatment of these patients remains an unmet medical need. Our findings indicate that blinatumomab therapy would not exclude a significant number of patients from the potential benefit of subsequent CD19-directed therapies such as chimeric antigen receptor T-cell therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Allografts
  • Antibodies, Bispecific / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B-Lymphocytes / chemistry
  • B-Lymphocytes / drug effects*
  • Combined Modality Therapy
  • Drug Resistance, Neoplasm
  • Drug Substitution
  • Female
  • Gene Expression Regulation, Leukemic
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Inotuzumab Ozogamicin
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Prognosis
  • Recurrence
  • Salvage Therapy
  • Treatment Failure
  • Young Adult

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • blinatumomab
  • Inotuzumab Ozogamicin