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

Document Type

Conference Proceeding

Publication Date

2-1-2024

Publication Title

Transplantation and Cellular Therapy

Abstract

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Volume

30

Issue

2

First Page

S29

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