Phase 1/2 study of high-dose palifermin for GVHD prophylaxis in patients undergoing HLA-matched unrelated donor HCT

医学 移植物抗宿主病 内科学 氟达拉滨 皮疹 胃肠病学 移植 环磷酰胺 免疫学 化疗
作者
Eduard Schulz,Lauren M. Curtis,Noa G. Holtzman,Jennifer Sponaugle,Kaska Wloka,Alen Ostojić,Alain Mina,Najla El Jurdi,Filip Pirsl,Ashley Carpenter,Mahshid Golagha,Arlene Sirajuddin,Theo Heller,Brian C. Shaffer,Frances T. Hakim,Jeffrey S. Rubin,Ronald E. Gress,Steven Z. Pavletic
出处
期刊:Blood [Elsevier BV]
卷期号:146 (8): 944-950 被引量:1
标识
DOI:10.1182/blood.2024028303
摘要

Abstract Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT). Palifermin, a recombinant N-truncated keratinocyte growth factor (KGF), protects epithelial tissues, including the thymus and gut. Although high-dose KGF prevents GVHD in preclinical models, lower doses of palifermin were ineffective in humans. We conducted a phase 1/2 trial evaluating high-dose palifermin for preventing severe chronic GVHD (CGVHD) in matched unrelated donor T-cell replete peripheral blood HCT after reduced-intensity conditioning (RIC). Using a 3+3 design, we determined the recommended phase 2 dose (RP2D), followed by an expansion phase. Palifermin (180-720 μg/kg) was given on day −7 before HCT. All 31 patients received fludarabine/cyclophosphamide RIC with tacrolimus, methotrexate, and sirolimus for GVHD prophylaxis. Palifermin was well tolerated, with self-limiting rash and pancreatic enzyme elevations as notable grade 3/4 adverse events. The RP2D was 720 μg/kg. Remarkably, no patients at this dose developed grade 2 to 4 acute GVHD (AGVHD [0/19]), although severe CGVHD rates (primary end point) remained unchanged compared to historical controls. Posttransplant lymphocyte phenotyping suggests palifermin modulates regulatory and naïve CD4+ T-cell numbers. These findings indicate that high-dose palifermin with RIC is safe and may prevent AGVHD, although it did not affect CGVHD rates in this study. This trial was registered at www.ClinicalTrials.gov as #NCT02356159.

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