CTLA-4 Blockade Following Relapse of Malignancy after Allogeneic Stem Cell Transplantation

Strategic Insights -

Researchers at the University of California conducted a phase I clinical trial to investigate the effect of CTLA-4 blockade by ipilimumab on graft-versus-malignancy (GVM) effects in patients with relapsed malignancy following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The study found that a single dose of ipilimumab increased CD4+ and CD4+HLA-DR+ T lymphocyte counts and intracellular CTLA-4 expression, but did not significantly change T regulatory cell numbers. The researchers concluded that further studies with multiple doses are needed to explore this phenomenon and correlate changes in lymphocyte subpopulations with clinical events.

Key Takeaways:

  • A phase I clinical trial was conducted to investigate the effect of CTLA-4 blockade by ipilimumab on GVM effects in patients with relapsed malignancy following allo-HSCT.
  • A single dose of ipilimumab increased CD4+ and CD4+HLA-DR+ T lymphocyte counts by 50% and 70% respectively in 20 of 29 patients.
  • Intracellular CTLA-4 expression in CD4+CD25(lo/-) T cells increased significantly after ipilimumab infusion.
  • The percentages of both CD4+CD25(high) and CD4+CD25(high)Foxp3+ T cells decreased significantly during the observation period, but the absolute cell counts did not change.
  • There was no consistent change in absolute lymphocyte count or in the number of T cells expressing the activation marker CD69.
  • The study concluded that further studies with multiple doses are needed to explore this phenomenon and correlate changes in lymphocyte subpopulations with clinical events.

Statistics:

  • 20 of 29 patients exhibited abnormally low lymphocyte counts (CD4 or/and CD8 T cells) before ipilimumab infusion.
  • 50% of the patients had abnormally low CD4+ T cell counts.
  • 70% of the patients had abnormally low CD8+ T cell counts.
  • 20 of 29 patients exhibited an elevated level of CD4+CD25(low) activated T cells at baseline.
  • 20 of 29 patients showed increases in CD4+CD25(low) T cells after ipilimumab infusion.
  • Intracellular CTLA-4 expression in CD4+CD25(lo/-) T cells increased by 50% after ipilimumab infusion.

Sources:

  • J. Zhou et al., University of California, Biology of Blood and Marrow Transplantation, 2011;17(5):682-92.
  • Science Letter, NewsRx.com, 2011.