Efficacy of the Addition of RGI-2001 to Tacrolimus and Methotrexate for Acute Gvhd Prevention in Myeloablative HSCT Using HLA-Matched Donors
Recommended Citation
Chen YB, Farhan S, Lekakis LJ, Schiller GJ, Yared JA, Assal A, Lee DD, Lane H, Gooley TA, DeFilipp Z, and Saad A. Efficacy of the Addition of RGI-2001 to Tacrolimus and Methotrexate for Acute Gvhd Prevention in Myeloablative HSCT Using HLA-Matched Donors. Transplant Cell Ther 2023; 29(2):S248-S249.
Document Type
Conference Proceeding
Publication Date
2-1-2023
Publication Title
Transplantation and Cellular Therapy
Abstract
Background: RGI-2001 is a liposomal glycolipid that binds the CD1d receptor of antigen-presenting cells (APC) resulting in activation of invariant natural killer (iNKT) cells. In the context of alloHCT, this interaction results in a cytokine-dependent Treg proliferation with potential modulation of the GvHD pathogenic cascade. Earlier dose-finding studies have shown that a single dose of RGI-2001 given on the day of alloHCT is safe and potentially contributed to prevention of acute GVHD (aGVHD).
Methods: RGI-2001-003 is an open-label, multi-center phase 2b study evaluating the efficacy and safety of RGI-2001 when added to a calcineurin inhibitor with methotrexate or mycophenolate mofetil (without T-cell depletion) for the prevention of aGvHD in subjects following myeloablative alloHCT. RGI-2001 was administered in a 30-minute infusion at a dose of 100 ug/kg IV weekly ×6 doses, starting on the day of transplant (Days 0, 7, 14, 21, 28, 35). The primary endpoint of the study is incidence of grades II-IV aGvHD by day 100.
Results: 49 subjects treated at 7 U.S. transplant centers were enrolled. Median age was 52 (range 21-65); 27 were male. Donors were 8/8 HLA-matched unrelated (n=32, 65%) 8/8 HLA-matched related (n=16, 33%), or 7/8 HLA-matched unrelated (n=1, 2%). The most common underlying diseases were AML (n=26, 53%), ALL (n=11, 22%), and MDS (n=8, 16%). Graft sources were PBSC (n=40) or BM (n=9). Common conditioning regimens were Bu/Flu (83%) and TBI/Cy (12.2%). All subjects received standard tacrolimus/methotrexate for GvHD prophylaxis. One infusion reaction (Grade 2) was reported. Treatment-emergent adverse events (TEAE >5%) related to RGI-2001 were stomatitis 14%, diarrhea 12%, nausea 12%, abdominal pain 8%, increased bilirubin 8%, ALT enzyme elevation 6%, ALP elevation 6%, and rash 6%. Grade 3 or 4 related TEAE >2% were stomatitis (6%), anemia (4%), and leukopenia (4%). Per protocol, patients were followed for a maximum of 1 year. The median follow-up of 46 survivors was 363 days (range, 164-365), and 46 of 49 patients had complete follow-up to day 180. Through day 100, there were 10 cases of grades II-IV aGvHD [20.4% (95% CI 10.2-34.3%)], two of which were grades III-IV [(4.1% (0.5-14.0%)]. One subject died at day 102 from aGvHD due to GI bleeding, 2 subjects died without aGvHD (at days 100 and 127). Figure 1 shows outcomes involving aGVHD by donor. Day-180 estimates of overall survival (OS) and grades II-IV aGvHD-free survival (aGFS) were 93.9% (82.2-98.0%) and 75.5% (60.9-85.3%), respectively. Figure 2 summarizes the probability of OS and aGFS as a function of time.
Conclusions: RGI-2001 added to the standard-of-care tacrolimus / methotrexate GvHD prophylaxis shows promising efficacy in the prevention of aGvHD for HLA-matched donors (related or unrelated) with an acceptable safety profile. A phase III study is planned.
Volume
29
Issue
2
First Page
S248
Last Page
S249