Results of Phase 2 Trial of Palifermin With Tacrolimus, Methotrexate, and Sirolimus GVHD Prophylaxis

By Dustin Samples - February 21, 2023

Keratinocyte growth factor (KGF) has previously been demonstrated to control both acute and chronic graft-versus-host disease (GVHD) in animal models. However, despite being FDA-approved, palifermin, a truncated form of human recombinant KGF, did not demonstrate the same results in human trials at the approved dose of 60μg/kg/day for 3 consecutive days.

The results of an open-label phase 2 trial (NCT02356159) were presented at the 2023 Tandem Transplant and Cellular Therapy Meetings of the ASTCT and CIBMTR. In this trial, a single, high dose of palifermin was evaluated for its effect on chronic GVHD when added to prophylaxis with tacrolimus, methotrexate, and sirolimus (TMS).

All patients received peripheral blood stem cell grafts from 8/8 HLA-matched unrelated donors, and all had cyclophosphamide and fludarabine as reduced-intensity conditioning prior to transplant. In phase 1, palifermin was given at 4 different dose levels, and the optimal suggested single dose for phase 2 was 720 μg/kg (DL4 from phase 1). Results of the patients who received any of 4 dose levels of palifermin (DL1, 180μg/kg; DL2 360μg/kg; DL3, 540μg/kg; or DL4) were retrospectively compared to the results of 31 patients who received identical TMS prophylaxis without palifermin as part of the NCT00520130 study.

There were no graft failures in the 28 patients enrolled and transplanted between 2015-2021. Cumulative incidence (CI) of chronic GVHD was 15.3% at 2 years, and CI of acute GVHD at days 100+ and 180+ was 7.1% and 10.7%, respectively. The estimated 5-year overall survival was 55.7%, non-relapse mortality was 25.3%, relapse-related mortality was 19.1%, and GVHD-related mortality was 5.1%.

Those receiving higher doses (DL3, DL4) of palifermin had lower CI of grade II-IV acute GVHD than the total cohort at both 100+ and 180+ days, but the CI of chronic GVHD did not significantly differ. Compared to those who received TRS without palifermin, DL3 and DL4 recipients had lower grade II-IV acute GVHD at days 100+ and 180+. The researchers did not observe any other differences in clinical outcomes.

Despite not significantly affecting the CI of chronic GVHD, higher doses of palifermin appeared to reduce the CI of grade II-IV acute GVHD in this study. Researchers speculate this effect may have been due to palifermin’s cytoprotective and anti-inflammatory properties.

Schulz E, Holtzman NG, Ostojic A, et al. Phase 2 Study of Single High-Dose Palifermin for Graft-Versus-Host Disease Prevention after Matched Unrelated Donor Transplantation. Abstract #338. Presented at the 2023 Tandem Meetings of ASTCT and CIBMTR; February 15-19, 2023; Orlando, FL.

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