Clinical trial update on bispecific antibodies, antibody-drug conjugates, and antibody-containing regimens for acute lymphoblastic leukemia

J Hematol Oncol. 2019 Feb 8;12(1):15. doi: 10.1186/s13045-019-0703-z.

Abstract

The relapse rate remains high after chemotherapy for adult patients with acute lymphoblastic leukemia (ALL). With better molecular diagnosis and classification as well as better assessment for minimal residual disease, major progress in the treatment for refractory and/or relapsed ALL is being made. In addition to the tyrosine kinase inhibitors (TKIs) for Philadelphia chromosome-positive ALL, immunotherapeutic agents, blinatumomab, inotuzumab ozogamicin (INO), and chimeric antigen receptor (CAR) T cells, are changing the treatment paradigm for ALL. Blinatumomab and INO are being incorporated into induction chemotherapy regimens and combined with TKIs for ALL therapy. A novel low-intensity regimen, miniHCVD-INO-blinatumomab, appears to be less toxic and more effective than conventional intensive chemotherapy regimens. This review summarized new therapeutic researches of ALL and updated latest progress in clinical trials on bispecific antibodies, antibody-drug conjugates, and new regimens incorporating these novel antibodies.

Keywords: Acute lymphoblastic leukemia; Antibody-drug conjugate; Bispecific antibody; Chimeric antigen receptor; Hyper-CVAD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Antibodies, Bispecific / therapeutic use*
  • Antigens, CD19 / immunology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • CD3 Complex / immunology
  • Clinical Trials as Topic
  • Female
  • Humans
  • Immunoconjugates / therapeutic use*
  • Inotuzumab Ozogamicin / therapeutic use*
  • Male
  • Molecular Targeted Therapy / methods*
  • Neoplasm, Residual / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Protein Kinase Inhibitors / therapeutic use*
  • Sialic Acid Binding Ig-like Lectin 2 / immunology

Substances

  • Antibodies, Bispecific
  • Antigens, CD19
  • CD19 molecule, human
  • CD22 protein, human
  • CD3 Complex
  • Immunoconjugates
  • Protein Kinase Inhibitors
  • Sialic Acid Binding Ig-like Lectin 2
  • blinatumomab
  • Inotuzumab Ozogamicin