Phase II, Open-Label Clinical Trial of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor for Life-Threatening Acute Graft-versus-Host Disease

Treatments that aid inflammation resolution, immune tolerance, and epithelial repair may improve outcomes beyond high-dose corticosteroids and other broad immunosuppressants for life-threatening acute graft-versus-host disease (aGVHD). We studied the addition of urinary-derived human chorionic gonadotropin/epidermal growth factor (uhCG/EGF; Pregnyl; Organon, Jersey City, NJ) to standard aGVHD therapy in a prospective Phase II clinical trial (ClinicalTrials.gov identifier NCT02525029). Twenty-two patients with Minnesota (MN) high-risk aGVHD received methylprednisolone 48 mg/m²/day plus 2000 units/m² of uhCG/EGF s.c. every other day for 1 week. Patients requiring second-line aGVHD therapy received uhCG/EGF 2000 to 5000 units/m² s.c. every other day for 2 weeks plus standard of care immunosuppression (physician's choice). Responding patients were eligible to receive maintenance doses twice weekly for 5 weeks. Immune cell subsets in peripheral blood were evaluated by mass cytometry and correlated with plasma amphiregulin (AREG) level and response to therapy. Most patients had stage 3-4 lower gastrointestinal tract GVHD (52%) and overall grade III-IV aGVHD (75%) at time of enrollment. The overall proportion of patients with a response at day 28 (primary endpoint) was 68% (57% with complete response, 11% with partial response). Nonresponders had higher baseline counts of KLRG1⁺ CD8 cells and T cell subsets expressing TIM-3. Plasma AREG levels remained persistently elevated in nonresponders and correlated with AREG expression on peripheral blood T cells and plasmablasts. The addition of uhCG/EGF to standard therapy is a feasible supportive care measure for patients with life-threatening aGVHD. As a commercially available, safe, and inexpensive drug, uhCG/EGF added to standard therapy may reduce morbidity and mortality from severe aGVHD and merits further study.