In this nonrandomized, open-label, phase I clinical trial ( Identifier: NCT02525029), 2 separate cohorts, each including 13 patients with aGVHD, were treated at a single institution with supplemental uhCG as an adjunct to standard immunosuppressive therapy. The cohorts were defined as those with high-risk aGVHD and those with steroid-dependent/refractory aGVHD of at least grade 2 severity who received uhCG in the first- and second-line settings, respectively. All patients were also treated with standard doses of corticosteroids for 14 days following diagnosis of aGVHD, which was tapered over 8 weeks in patients demonstrating a response, as well as bacterial, viral, and antifungal prophylaxis according to institution guidelines. 

The primary study endpoint was determination of maximum tolerated dose (MTD) in each study arm, with uhCG administered subcutaneously at 3 dosage levels from 500 units uhCG/m2 to 2000 units uhCG/m2 within each cohort, although the dosing schedules varied depending on study cohort. Secondary study endpoints included safety and the proportions of surviving patients responding to treatment at days 7, 14, 28, and 56.

Both study cohorts had a median age of 65 years at baseline, although median Karnofsky performance status score was 70 for patients treated with uhCG in the first-line setting and 30 for those with steroid-dependent/refractory aGVHD. Grade 3/4 lower gastrointestinal aGVHD was observed in 69.3% and 84.7% of participants in these 2 respective groups.

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Regarding safety, no grade 4 or 5 or dose-limiting toxicities were reported in either cohort.

Rates of CR at day 28 following administration of uhCG were 62% and 54% for those receiving this treatment in the first- and second-line setting, respectively. Of the 4 deaths that occurred in the latter cohort by day 28, 3 were attributed to aGVHD and 1 was reported to be caused by relapsed malignancy.

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Notably, serial assessments of plasma EGF following administration of uhCG showed a temporal increase in EGF that peaked at 6 hours postdose in those treated in the first-line setting, although no increase in circulating EGF was seen for those with steroid dependent/refractory aGVHD.

“This observation led us to the hypothesis that EGF may be rapidly taken up into immune cells and tissues and not remain free for circulation when damage is more extensive,” the study authors noted.

Also observed was a greater than 2-fold increase in the ratio of Tregs to conventional T cells (Tcons) at day 7 of uhCG therapy that gradually returned to baseline as dosing became less frequent and was ultimately discontinued.

“Our study of uhCG as supportive care of life-threatening aGVHD will continue in phase 2, where we can more concretely estimate the response rates and magnitude of clinical benefit,” the study authors noted in their concluding remarks.


Holtan SG, Hoeschen AL, Cao Q, et al. Facilitating resolution of life-threatening acute GVHD with human chorionic gonadotropin and epidermal growth factor. Blood Adv. 2020;4(7):1284-1295.