Targeting interleukin-2 to the bone marrow stroma for therapy of acute myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation

Cancer Immunol Res. 2015 May;3(5):547-56. doi: 10.1158/2326-6066.CIR-14-0179. Epub 2015 Feb 11.

Abstract

The antibody-based delivery of IL2 to extracellular targets expressed in the easily accessible tumor-associated vasculature has shown potent antileukemic activity in xenograft and immunocompetent murine models of acute myelogenous leukemia (AML), especially in combination with cytarabine. Here, we report our experience with 4 patients with relapsed AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were treated with the immunocytokine F16-IL2, in combination with low-dose cytarabine. One patient with disseminated extramedullary AML lesions achieved a complete metabolic response identified by PET/CT, which lasted 3 months. Two of 3 patients with bone marrow relapse achieved a blast reduction with transient molecular negativity. One of the 2 patients enjoyed a short complete remission before AML relapse occurred 2 months after the first infusion of F16-IL2. In line with a site-directed delivery of the cytokine, F16-IL2 led to an extensive infiltration of immune effector cells in the bone marrow. Grade 2 fevers were the only nonhematologic side effects in 2 patients. Grade 3 cytokine-release syndrome developed in the other 2 patients but was manageable in both cases with glucocorticoids. The concept of specifically targeting IL2 to the leukemia-associated stroma deserves further evaluation in clinical trials, especially in patients who relapse after allo-HSCT.

Publication types

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

MeSH terms

  • Adult
  • Antibodies, Monoclonal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow / immunology*
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Interleukin-2 / administration & dosage
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / immunology
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / administration & dosage
  • Recurrence
  • Tenascin / immunology
  • Transplantation, Homologous

Substances

  • Antibodies, Monoclonal
  • Interleukin-2
  • Recombinant Fusion Proteins
  • Tenascin