Background
Prospective, multicenter, open-label randomized phase III trial in China. N=190 (of 251 screened), adults 18–60 with hematologic malignancies receiving myeloablative haploidentical or unrelated-donor HSCT with ATG-based GVHD prophylaxis. Sitagliptin (DPP-4 inhibitor) added to prophylaxis to reduce acute GVHD.
Results
Interventions and follow up: Arm A: ATG + calcineurin inhibitor + methotrexate + MMF, plus sitagliptin 600 mg PO q12h, days −1 to +14
Arm B: ATG + calcineurin inhibitor + methotrexate + MMF alone
Primary endpoint: Cumulative incidence of grade II–IV aGVHD by day +100
mFollow up: 29.8 months (range 0.7–41.3)
Results: Grade II–IV aGVHD, d+100 (primary): 14.7% vs 31.6%; sHR 0.41; P=.005
Grade III–IV aGVHD (exploratory): 6.3% vs 18.9%; sHR 0.30; P=.010
Intestinal aGVHD (exploratory): 12.6% vs 29.5%; P=.004
GRFS, d+180 (exploratory): 86.3% vs 72.6%; HR 0.44; P=.016
2-yr cGVHD, NRM, RFS, OS: no significant between-group differences
Relapse, engraftment, CMV/EBV reactivation: no difference
Arm B: ATG + calcineurin inhibitor + methotrexate + MMF alone
Primary endpoint: Cumulative incidence of grade II–IV aGVHD by day +100
mFollow up: 29.8 months (range 0.7–41.3)
Results: Grade II–IV aGVHD, d+100 (primary): 14.7% vs 31.6%; sHR 0.41; P=.005
Grade III–IV aGVHD (exploratory): 6.3% vs 18.9%; sHR 0.30; P=.010
Intestinal aGVHD (exploratory): 12.6% vs 29.5%; P=.004
GRFS, d+180 (exploratory): 86.3% vs 72.6%; HR 0.44; P=.016
2-yr cGVHD, NRM, RFS, OS: no significant between-group differences
Relapse, engraftment, CMV/EBV reactivation: no difference
Adverse events
Overall: adverse event profiles similar between arms
Infection: CMV/EBV reactivation not increased
Grade ≥3 rates: NR in abstract
Infection: CMV/EBV reactivation not increased
Grade ≥3 rates: NR in abstract
Conclusions
Adding sitagliptin to ATG-based prophylaxis significantly reduced grade II–IV aGVHD after alternative-donor HSCT without increasing relapse or infection. Reductions in severe and intestinal aGVHD and day +180 GRFS were exploratory; no long-term GRFS, RFS or OS benefit was shown.
Key Limitations
Open-label; modest N (190) from Chinese centers, ATG-based regimens and myeloablative conditioning in patients 18–60 only, limiting generalizability (e.g., PTCy-based platforms, older or reduced-intensity patients). Severe aGVHD and GRFS findings are exploratory; no OS/RFS/cGVHD benefit, so the clinical impact beyond aGVHD reduction is unproven. Single DPP-4 inhibitor dose schedule.
Clinical Context
Adds randomized evidence for DPP-4 inhibition (sitagliptin) as an oral aGVHD prophylaxis adjunct in ATG-based regimens, an off-label repurposed drug for this indication. Abatacept is FDA-approved for aGVHD prophylaxis in unrelated-donor HSCT; no head-to-head or PTCy-platform data exist for sitagliptin. Needs validation outside China and in PTCy-based transplants.
