In a study published by Magenau et al in the journal Blood Advances, researchers found that patients with high-risk acute myeloid leukemia (AML) who received a form of type I interferon after allogeneic hematopoietic stem cell transplant experienced reduced rates of disease relapse. Additionally, treatment with the agent did not result in any increased toxicity.
Previous laboratory studies by the research group suggested the drug interferon could enhance function of a key subset of dendritic cells that can selectively enhance T cells, which recognize and kill leukemia cells after transplant. Interferon alfa is used in some autoimmune diseases, but the response does not last long. To get around that, researchers looked at a long-acting form of interferon—pegylated interferon alfa—which is commercially available to treat hepatitis B and C, as well as some blood cancers.
Study Findings
An early-stage clinical trial enrolled 36 patients (median age = 60 years) who received four doses of peginterferon alfa every 14 days beginning just before their transplant. At 6 months, 39% of patients had relapsed, reducing the disease relapse rate by over 20%. Additionally, this rate was sustained through 1 year posttransplantation. The drug was generally well tolerated, with side effects in line with what many transplant patients experience. The incidence of transplant-related mortality was 13%, and severe grade III to IV acute graft-vs-host disease occurred in 11% of patients.
“Despite the curative potential of bone marrow transplant, relapse remains the greatest barrier to successful outcomes. This result suggests that a brief course of peginterferon alfa may increase the antileukemic potency of an allogeneic transplant. If this intervention can reduce relapse, even by 10% to 20%, it could translate into improved survival,” said lead study author John Magenau, MD, Clinical Associate Professor of Internal Medicine at Michigan Medicine.
Although more research is needed to confirm the findings in a larger, randomized clinical trial, the researchers noted that new strategies are essential for this group of patients who have few options. The team has some ideas based on ongoing laboratory research to try to improve upon these results. In addition, they are looking to perform a randomized trial, potentially also exploring interferon in other types of transplants or blood cancers.
The study authors concluded, “Paired blood samples from donors and recipients after hematopoietic stem cell transplant indicated elevated levels of type I interferon with cellular response, persistence of cross-presenting dendritic cells and circulating leukemia antigen–specific T cells. These data suggest that prophylactic administration of pegylated [interferon alfa] is feasible in the perihematopoietic stem cell transplant period. In high-risk AML, increased toxicity was not observed with preliminary evidence for reduction in leukemia relapse after [transplant].”
Funding: This study was funded by the National Institutes of Health and the Elsa U. Pardee Foundation. For full disclosures of the study authors, visit ashpublications.org/bloodadvances.
