High-dose palifermin for GvHD prophylaxis: Results from a phase I/II trial

Palifermin, a recombinant N-truncated keratinocyte growth factor, has been shown to protect epithelial tissues, such as in the thymus and gut. While high doses of keratinocyte growth factor have prevented GvHD in preclinical models, lower doses of palifermin have thus far been ineffective in human trials. 

A phase I/II trial (NCT02356159) evaluated high doses of palifermin for GvHD prophylaxis in patients undergoing matched unrelated donor T-cell peripheral-blood HSCT. The trial determined the recommended phase II dose of palifermin, followed by an expansion phase assessing its impact on severe cGvHD at 2 years vs a historical rate of 28%, with a phase II primary endpoint of 2-year severe cGvHD cumulative incidence. Exploratory objectives included effects on immune reconstitution, thymic function, aGvHD, survival, NRM, and relapse rates. Palifermin was given on Day −7 before HSCT at doses between 180 μg/kg and 720 μg/kg. In total, 31 patients were enrolled, with results published in Blood by Schulz et al. 

Key learnings

Palifermin was generally well tolerated. Notable Grade 3/4 AEs were self-limiting rash and pancreatic enzyme elevations (most resolved without intervention). The recommended phase II dose was determined at 720 μg/kg, which was administered to 19 patients.

Palifermin significantly reduced aGvHD and at 720 μg/kg, no patients developed Grade II–IV aGvHD vs 19% in the control group. The phase II primary endpoint of severe cGvHD rate did not differ compared with historical controls.

At 5-year follow-up, OS was 56% in patients receiving palifermin vs 52% for TMS controls. Primary disease relapse was the main cause of death in 71% of the palifermin efficacy cohort. Post-transplant lymphocyte phenotyping suggests palifermin modulated T-reg and naïve CD4+ T-cell numbers.

These findings indicate that high-dose palifermin is safe and effective for prophylaxis of aGvHD, although it did not impact on cGvHD rates. Additional trials could investigate palifermin in combination with other GvHD prophylaxis strategies.