11.23.21

Type 1 IFN Feasibility in Peri-HCT Period

Magenau JM, Peltier DC, Riwes M, et al. Type-1 Interferon to Prevent Leukemia Relapse after Allogeneic Transplantation. Blood Advances. 2021; (doi: 10.1182/bloodadvances.2021004908).

Preliminary evidence from a proof-of-concept Phase I/II clinical trial suggests long-acting Type-1 interferon (pegIFNα) can be prophylactically administered during the peri-transplant period of allogeneic hematopoietic cell transplantation (HCT). This can potentially reduce leukemic relapse without elevating toxicity in patients with high-risk acute myeloid leukemia (AML). Previous preclinical studies found IFNα increased cross-presentation of leukemia specific antigens by CD8α dendritic cells (DCs) and intensified graft-versus-leukemia (GVL) response. In this trial, 36 patients with treatment-resistant AML not in remission or poor risk leukemia received four pegIFNα dosages in two-week intervals starting one day before HCT. Serious adverse events rated grade 3 or higher were observed in 25% of patients, establishing a maximum tolerated dose of 180 mcg. A 39% relapse recurrence rate was seen at 9 months in Phase II, persisting through one year post-HCT. In all, 13% of patients experienced transplant-related mortality, and 11% developed severe grade III-IV acute GVHD. Type-1 IFN with cellular response, lingering cross-presenting DCs, and circulating leukemia antigen-specific T cells were detected in post-HCT paired blood samples from donors and recipients.

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