Type 1 interferon to prevent leukemia relapse after allogeneic transplantation

Area of Science:

• Immunology
• Hematology
• Oncology

Background:

• Relapse remains a significant challenge after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML).
• Preclinical studies indicated that type 1 interferon-alfa (IFN-α) enhances graft-versus-leukemia (GVL) responses by improving antigen presentation.
• Pegylated interferon-alfa (pegIFNα), a long-acting form of IFN-α, was investigated for its potential to augment GVL and reduce relapse.

Purpose of the Study:

• To evaluate the safety and feasibility of prophylactic pegIFNα administration in patients undergoing HCT for high-risk AML.
• To determine the maximum tolerated dose (MTD) of pegIFNα in this setting.
• To assess the preliminary efficacy of pegIFNα in reducing leukemia relapse post-HCT.

Main Methods:

• A phase 1/2 clinical trial administered pegIFNα (4 dosages every 14 days, starting day -1 pre-HCT) to patients with high-risk AML.
• Dose selection utilized an adaptive design to assess dose-limiting toxicities.
• Efficacy was measured by the 6-month incidence of relapse at the MTD; immunological correlates were also analyzed.

Main Results:

• The MTD of pegIFNα was established at 180 μg, with grade 3 or higher adverse events occurring in 25% of patients.
• The 6-month incidence of relapse was 39%, sustained through 1 year post-HCT. Transplant-related mortality was 13%, and grade III-IV acute graft-versus-host disease (GVHD) was 11%.
• Post-HCT analysis revealed elevated type 1 IFN levels, persistent cross-presenting dendritic cells (DCs), and circulating leukemia antigen-specific T cells.

Conclusions:

• Prophylactic peri-HCT administration of pegIFNα is feasible and appears safe in high-risk AML patients.
• Preliminary data suggest a potential reduction in leukemia relapse after HCT without increased toxicity.
• The observed immunological changes support the mechanism of enhanced GVL response.