Post-Transplant Cyclophosphamide and Urinary-Derived Human Chorionic Gonadotropin and Epidermal Growth Factor (uhCG/EGF) As Graft Versus Host Disease Prophylaxis for Mismatched Unrelated Donor Transplantation: A Phase I Dose Escalation Study (PTCY2HCG3)

Document Type

Conference Proceeding

Publication Date

2-1-2026

Publication Title

Transplant Cell Ther

Keywords

CD3 antigen, CD4 antigen, chorionic gonadotropin, cyclophosphamide, epidermal growth factor, immunoglobulin G, mycophenolate mofetil, mycophenolic acid, tacrolimus, acute graft versus host disease, adult, African American, aged, Caucasian, chimera, chronic graft versus host disease, chronic myelomonocytic leukemia, clinical article, cohort analysis, conference abstract, controlled study, cytokine release syndrome, cytomegalovirus pneumonia, drug therapy, engraftment, febrile neutropenia, female, fever, follow up, graft failure, graft rejection, graft versus host reaction, human, immunological tolerance, low drug dose, male, microchimerism, mismatched unrelated donor, neutrophil, phase 1 clinical trial, pregnancy, prophylaxis, regulatory T lymphocyte, relapse, side effect, special situation for pharmacovigilance, T cell lymphoma

Abstract

PTCy is a great step forward in preventing GVHD but the optimal combination of drugs to add to PTCy is not yet defined. Kanakry and his team previously demonstrated that PTCy efficacy is dependent on Treg. Human chorionic gonadotropin (hCG) has been shown to induce immune tolerance and significantly increase Treg cells. Some studies using urinary-derived hCG and epidermal growth factor (uHCG/EGF) in acute and chronic GVHD treatment have shown some clinical success. We hypothesized that the addition of low dose uhCG/EGF after PTCy for MMUD PB SCT can be well tolerated and could help prevent GVHD via 2 potential mechanisms: increase T regs similar to its role in pregnancy and supplementation of epidermal growth factor to help repair of damaged epithelial tissue post conditioning. The reason to use low-dose hCG is based on the idea that symptoms of auto-inflammatory disease relieve very early in pregnancy Methods: This is a single center phase 1 study. Eligible patients received PTCy 50mg/kg D+3, +4 and uhCG/EGF that was administered Sub-cutaneously on day+7, +9 and +11. Tacrolimus and mycophenolate were started on day+5. Following 3+3 design, the plan to enroll patients in cohorts of 3, at uhCG/EGF dose escalations of 250, 500 and 1000 IU. No dose escalation of uhCG/EGF beyond 1000 IU per day. Here we report the results of 4 patients who were enrolled so far. Results: Patients enrolled were 3 females and 1 male. 1 African American and 3 Caucasians. Median age was 64.5 (61-68). Donors were all MMUD with median age of 33. Two patients had AML, one had T-NHL, and one had CMML. CMV recipient status positive in all except1. HCT-CI was >=3 in 2 patients. Median CD34 and CD3 infused were 3.045 × 106 and 1.8 × 108/kg recipient respectively. All 4 patients received 3 doses of uhCG/EGF without any DLT by day +35. The first 3 pts received 3 doses of 250 IU and one patient received 3 doses of 500 IU. 2 patients had cytokine release syndrome (CRS) with ASTCT grade of 1. 1 patient had neutropenic fever, and no patient had engraftment fever. Median neutrophils and platelets engraftment were 15 and 23 days respectively. Chimerism post SCT was ≥100% donor at day 30 for all patients. No graft failure. Median time to follow up is 642 days. One patient died because of CMML with very proliferative disease before SCT. All other patients are alive without relapse. Acute GVHD grade II developed in 1 patient, none had grade III-IV. 2 pts had mod cGVHD and TMA requiring treatment. One patient had CMV pneumonia, while on steroids for treatment of aGVHD, resolved. At last follow up for 3 evaluable patients IgG were >400 mg/dl and CD4 > 200 cells/ul. Conclusions: Cy2HCG3 post PB MMUD-SCT was well tolerated in this small number of patients in an ongoing phase I dose escalation study. HCG did not affect engraftment so far. We did not observe high grade CRS, and no DLT. These results are encouraging. The trial is ongoing. (ClinicalTrials.gov ID: NCT04886726)

Volume

32

Issue

2

First Page

S278

Last Page

S279

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