RGI-2001 with CNI-Based Prophylaxis Demonstrates Better Acute Gvhd-Free Survival Following Myeloablative Allohct without Increased Relapse: Comparison of a Multi-Center Phase 2b Study with a Contemporaneous CIBMTR Cohort

Despite the use of prophylactic immunosuppressive therapy, acute graft-versus-host disease (aGVHD) has historically occurred in 40-60% of subjects following allogeneic hematopoietic cell transplantation (HCT); severe cases represent a major cause of morbidity and mortality. RGI-2001 is a liposomal glycolipid that binds the CD1d receptor of antigen-presenting cells resulting in activation of invariant natural killer cells and regulatory T cell proliferation that leads to host-specific tolerance in the transplanted donor cells. Repeat dosing of RGI-2001 in RGI-2001-003 was shown to be safe with no serious infusion reactions or related SAEs and low rates of aGVHD (Blood. 2022;140(S1): 1877–1878). Here we compare GVHD, relapse, and survival outcomes to a contemporaneous CIBMTR cohort that did not receive RGI-2001. RGI-2001-003, an open-label Phase 2b study, evaluated RGI-2001 added to a calcineurin inhibitor (CNI) with methotrexate (MTX) or mycophenolate mofetil for the prevention of aGVHD following myeloablative HCT (without T-cell depletion). PTCy and ATG were prohibited. RGI-2001 100 µg/kg was infused weekly × 6, starting on the day of HCT. The primary endpoint was grade II-IV aGVHD by Day 100. A cohort was obtained from CIBMTR using the same eligibility criteria. The primary and key secondary endpoints were compared between groups using logistic regression. Comparisons of preliminary data were performed on 48 RGI-2001 subjects (median age 52 yrs) and 207 CIBMTR subjects (median age 50 yrs) who received HCT from a matched related or unrelated donor at the same 7 U.S. centers from 11/2019-11/2021 and 1/2018-10/2019, respectively. The majority were transplanted for AML (RGI 54%, CIBMTR 52%) or ALL (23%, 27%) from an 8/8 URD (67%, 61%) and received PBSCs (81%, 83%). All RGI and 99% of CIBMTR subjects received tacrolimus (tac)/MTX; there were no graft failures. Grade II-IV aGVHD was lower, and overall and aGVHD-free survival were each higher in the RGI-2001 group. Relapse was not increased and chronic GVHD was similar (Table 1; Figure 1). RGI-2001 added to tac/MTX resulted in less aGVHD without an increase in relapse compared to a CIBMTR cohort. RGI-2001 demonstrates a potential role in aGVHD prophylaxis in the myeloablative HCT setting. A Phase 3 study is planned.