A recently published study by Magenau et al in the journal Blood Advances reported that high-risk acute myeloid leukemia (AML) patients who received interferon treatment after allogeneic hematopoietic cell transplantation (HCT) showed reduction in relapse rate of disease.
Earlier studies have suggested that drug interferon can enhance function of a subset of dendritic cells (DC) which further selectively enhance T-cells. These T-cells can recognize and kill leukemia cells after transplant. Such use of interferon-alpha has been applied in few autoimmune diseases; however, the duration of the response is very short. To overcome this limitation, the researchers looked at a long-acting form of commercially available form of interferon: pegylated interferon alfa (pegIFNα), used for treating hepatitis B and C, along with some types of blood cancer.
The early-stage clinical trial enrolled 36 treatment resistant AML not in remission or poor risk leukemia patients with a median age of 60 years. All the patients received four dosages of pegIFNα every two weeks beginning just before bone marrow transplant. Efficacy of treatment was determined by six-month incidence of relapse at maximum tolerated dose (MTD). At 6 months, the disease relapse rate was reduced by over 20% (39% incidence of relapse). Importantly, this rate was sustained over a period of one year post-transplant. The drug was very well tolerated, and no new safety concerns were reported during the study. The adverse events (AE) included transplant-related mortality (13%) and severe grade III to IV acute graft-vs-host disease (11%).
“Despite the curative potential of bone marrow transplants, 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 bone marrow transplant. If this intervention can reduce relapse, even by 10% to 20%, it could translate into improved survival,” said the first author of study, John Magenau, MD, Clinical Associate Professor of Internal Medicine at Michigan University.
The authors concluded that “Paired blood samples from donors and recipients after HCT indicated elevated levels of Type-1 IFN with cellular response, persistence of cross-presenting DCs and circulating leukemia antigen specific T-cells. These data suggest that prophylactic administration of pegIFNα is feasible in the peri-HCT period. In high-risk AML, increased toxicity was not observed with preliminary evidence for reduction in leukemia relapse after HCT.”
Magenau JM, Peltier DC, Riwes M, Pawarode A, Parkin B, Braun TM, Anand S, Ghosh M, Maciejewski J, Yanik GA, Choi SW, Talpaz M, Reddy P. Type-1 Interferon to Prevent Leukemia Relapse after Allogeneic Transplantation. Blood Adv. 2021 Oct 4: blood advances.2021004908. doi: 10.1182/bloodadvances.2021004908.