Immunological response induced by abagovomab as a maintenance therapy in patients with epithelial ovarian cancer: relationship with survival-a substudy of the MIMOSA trial

Cancer Immunol Immunother. 2014 Oct;63(10):1037-45. doi: 10.1007/s00262-014-1569-0. Epub 2014 Jun 21.

Abstract

Purpose: To determine whether abagovomab induces protective immune responses in ovarian cancer patients in first clinical remission. The present analysis is a substudy of monoclonal antibody immunotherapy for malignancies of the ovary by subcutaneous abagovomab trial (NCT00418574).

Methods: The study included 129 patients, 91 in the abagovomab arm and 38 in the placebo arm. Circulating CA125-specific cytotoxic T lymphocytes (CTL) were measured by a flow cytometry-based interferon-γ producing assay. Human antimouse antibody and anti-anti-idiotypic (Ab3) were assessed by ELISA. Patients were evaluated before starting the treatment and at different time points during induction and maintenance phases.

Results: A similar percentage of patients in both the placebo and abagovomab arms had CA125-specific CTL (26.3 and 31.8 %, respectively; p = 0.673 by Fisher's exact test). Patients with CA125-specific CTL in both arms tended to have an increased relapse-free survival (RFS, log-rank test p = 0.095) compared to patients without. Patients (n = 27) in the abagovomab arm without CA125-specific CTL but that developed Ab3 above the cutoff (defined as median Ab3 level at week 22) had a prolonged RFS compared to patients (n = 24) that did not develop Ab3 above the cutoff (log-rank test p = 0.019).

Conclusion: Abagovomab does not induce CA125-specific CTL. However, patients with CA125-specific CTL perform better than patients without, irrespective of abagovomab treatment. Abagovomab-induced Ab3 associate with prolonged RFS in patients without CA125-specific CTL. Further studies are needed to confirm these data and to assess the potential utility of these immunological findings as a tool for patient selection in clinical trial.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • CA-125 Antigen / immunology*
  • Carcinoma, Ovarian Epithelial
  • Disease-Free Survival
  • Double-Blind Method
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Humans
  • Immunotherapy
  • Membrane Proteins / immunology*
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / immunology*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / immunology*
  • Survival Analysis
  • T-Lymphocytes, Cytotoxic / immunology*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • CA-125 Antigen
  • Epitopes, T-Lymphocyte
  • MUC16 protein, human
  • Membrane Proteins
  • abagovomab

Associated data

  • ClinicalTrials.gov/NCT00418574