Dertschnig, Simone and Gergely, Peter and Finke, Jurgen and Schanz, Urs and Holler, Ernst and Holtick, Udo and Socie, Gerard and Medinger, Michael and Passweg, Jakob and Teshima, Takanori and Stylianou, Christos and Oehen, Stephan and Heim, Dominik and Bucher, Christoph (2023) Mocravimod, a Selective Sphingosine-1-Phosphate Receptor Modulator, in Allogeneic Hematopoietic Stem Cell Transplantation for Malignancy. TRANSPLANTATION AND CELLULAR THERAPY, 29 (1). 41e1-41e9. ISSN 2666-6375, 2666-6367
Full text not available from this repository. (Request a copy)Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the sole curative option for patients with acute myelogenous leukemia. Outcomes are limited by leukemia relapse, graft-versus-host disease (GVHD), and abnormal immune reconstitution. Mocravimod (KRP203) is an oral sphingosine-1-phosphate receptor (S1PR) modulator that blocks the signal required by T cells to egress from lymph nodes and other lym-phoid organs. Mocravimod retains T cell effector function, a main differentiator to immunosuppressants. In pre -clinical models, mocravimod improves survival by maintaining graft-versus-leukemia (GVL) activity while reducing GVHD. In patients undergoing allo-HSCT for hematological malignancies, mocravimod is postulated to prevent GVHD by redistributing allogeneic donor T cells to lymphoid tissues while allowing a sufficient GVL effect in the lymphoid, where malignant cells usually reside. The primary objective of this study was to assess the safety and tolerability of mocravimod in patients undergoing allo-HSCT for hematologic malignancies. Sec-ondary objectives were to determine the pharmacokinetic profiles of mocravimod and its active metabolite mocravimod-phosphate in this patient group, as well as to assess GVHD-free, relapse free survival at 6 months after the last treatment. In this 2-part, single-and 2-arm randomized, open-label trial, we evaluated the safety, tolerability, and pharmacokinetics of mocravimod in allo-HSCT recipients (ClinicalTrials.gov identifier NCT01830010). Patients received either 1 mg or 3 mg mocravimod per day on top of standard of care GVHD pro-phylaxis with either cyclosporine A/methotrexate or tacrolimus/methotrexate. We found that mocravimod can be safely added to standard treatment regimens in patients with hematologic malignancies requiring allo-HSCT. Mocravimod resulted in a significant reduction of circulating lymphocyte numbers and had no negative impact on engraftment and transplantation outcomes. Our results indicate that mocravimod is safe and support a larger study to investigate its efficacy in a homogeneous acute myelogenous leukemia patient population undergoing allo-HSCT. (C) 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; BONE-MARROW; MULTIPLE-SCLEROSIS; DOUBLE-BLIND; T-CELLS; FTY720; FINGOLIMOD; SAFETY; Mocravimod; Graft-versus-host disease; Graft-versus-leukemia; Allogeneic HSCT; S1PR modulator |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jan 2024 10:42 |
| Last Modified: | 30 Jan 2024 10:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60802 |
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