Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia

Cancer Sci. 2020 Apr;111(4):1314-1323. doi: 10.1111/cas.14322. Epub 2020 Feb 11.

Abstract

Adult patients with relapsed/refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) have a poor prognosis. Blinatumomab is a bispecific T-cell engager (BiTE) immuno-oncology therapy with dual specificity for CD19 and CD3 that redirects patients' CD3-positive cytotoxic T cells to lyse malignant and normal B cells. We conducted an open-label, phase 1b/2 study to determine the safety, pharmacokinetics, efficacy and recommended dose of blinatumomab in Japanese adults with R/R B-precursor ALL. Patients received 9 μg/day blinatumomab during week 1 and 28 μg/day during weeks 2-4, with a 2-week treatment-free interval (6-week cycle); patients received 28 μg/day blinatumomab in subsequent cycles. Primary endpoints were the incidence of dose-limiting toxicities (DLT) in phase 1b and complete remission (CR)/CR with partial hematologic recovery (CRh) within the first two cycles in phase 2. A total of 26 patients enrolled and 25 (96%) reported grade ≥3 adverse events (mostly cytopenias). There were no DLT. CR/CRh within two cycles was achieved by 4 of 5 patients (80%) in phase 1b and 8 of 21 patients (38%) in phase 2. Among patients with evaluable minimal residual disease, 4 (100%) in phase 1b and 3 (38%) in phase 2 had a complete MRD response. Median RFS for 8 patients who achieved CR/CRh in phase 2 was 5 (95% CI: 3.5-6.4) months; median OS was not estimable. There were no significant associations between maximum cytokine levels or percentage of specific cell types during cycle 1 and response. Consistent with global studies, blinatumomab appeared to be safe and efficacious in Japanese adults with R/R ALL.

Keywords: Japan; acute lymphoblastic leukemia; blinatumomab; clinical study; phase 1b; refractory; relapsed.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Bispecific / administration & dosage*
  • Antibodies, Bispecific / adverse effects
  • Antibodies, Bispecific / blood
  • Antibodies, Bispecific / pharmacokinetics
  • Antigens, CD19 / genetics
  • Antigens, CD19 / immunology
  • B-Lymphocytes / pathology
  • CD3 Complex / genetics
  • CD3 Complex / immunology
  • Dexamethasone / administration & dosage
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Interferon-gamma / blood
  • Kaplan-Meier Estimate
  • Lymphoma, B-Cell / blood
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / pathology
  • Male
  • Middle Aged
  • Neoplasm, Residual / blood
  • Neoplasm, Residual / drug therapy*
  • Neoplasm, Residual / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Remission Induction
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Bispecific
  • Antigens, CD19
  • CD3 Complex
  • IFNG protein, human
  • blinatumomab
  • Dexamethasone
  • Interferon-gamma

Grants and funding