ASH 2018 | Phase I study of HCG/EGF adjunct therapy in high-risk and steroid refractory acute graft-versus-host disease

On Saturday 1 December 2018, an oral abstract session took place at the 60^th American Society of Hematology (ASH) Annual Meeting in San Diego, CA. During Session: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: GVHD Grading and Outcomes and Management, Abstract #71 was presented by Shernan G. Holtan, University of Minnesota, Minneapolis, MN, USA, entitled: Facilitating Resolution of Life-Threatening Acute Graft-Versus-Host Disease By Supplementation of Human Chorionic Gonadotropin (hCG) and Epidermal Growth Factor (EGF) (Pregnyl): A Phase I Study.

This phase I study was conducted to evaluate hCG/EGF in patients with Minnesota High Risk and steroid dependent or refractory acute graft-versus-host disease (aGvHD) to improve both hCG-mediated immunologic tolerance and tissue repair via supplemental EGF. Urinary-derived hCG (Pregnyl®) was given to patients with aGvHD in addition to standard of care.

Patients and methods

N = 26 patients

• Arm 1: N = 13 patients (median age = 65 years) were high-risk and received first line Pregnyl® SQ QOD for 7 days
• Arm 2: N = 13 patients (median age = 65 years) were steroid refractory and received Pregnyl® as second line treatment SQ QOD for 14 days

Key findings

• hCG/EGF was well tolerated, with no dose-limiting toxicities
• Median EGF dose: 50,833 pg/ml
• Most common treatment emergent adverse event was edema in 16 patients (62%)
• Proportion of day-28 response
  • Arm 1:
    • CR: 62%
    • PR: 0
    • NR: 38%
  • Arm 2:
    • CR: 54%
    • PR: 8%
    • NR: 38%
  • Pregnyl® does not worsen cytopenias
  • Pregnyl® increases serum hCG, estradiol, and testosterone; all returned to baseline by day 56
  • Pregnyl® may support Treg/Tcon ratio
  • AREG significantly decreases over time in patients with day-28 CR/PR

In conclusion, Pregnyl® appears “safe and feasible supportive care in first and second line severe aGvHD.” Pregnyl® may facilitate tolerance and tissue repair, without adding to side-effects of GvHD treatment. Doctor Holtan added that “the optimal dose and duration of hCG/EGF are under investigation, with ongoing dose escalation in patients with steroid-refractory aGvHD based upon these initial results.”