1. Combination of dociparstat sodium (DSTAT), a CXCL12/CXCR4 inhibitor, with azacitidine for the treatment of hypomethylating agent refractory AML and MDS.
- Author
-
Huselton E, Rettig MP, Campbell K, Cashen AF, DiPersio JF, Gao F, Jacoby MA, Pusic I, Romee R, Schroeder MA, Uy GL, Marcus S, and Westervelt P
- Subjects
- Aged, Aged, 80 and over, Anticoagulants therapeutic use, Antimetabolites, Antineoplastic therapeutic use, Biomarkers, Tumor, Chemokine CXCL12 antagonists & inhibitors, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes pathology, Pilot Projects, Prognosis, Receptors, CXCR4 antagonists & inhibitors, Survival Rate, Azacitidine therapeutic use, DNA Methylation, Drug Resistance, Neoplasm drug effects, Gene Expression Regulation, Neoplastic drug effects, Heparin therapeutic use, Leukemia, Myeloid, Acute drug therapy, Myelodysplastic Syndromes drug therapy
- Abstract
Leukemia stem cells utilize cell adhesion molecules like CXCR4/CXCL12 to home to bone marrow stromal niches where they are maintained in a dormant, protected state. Dociparstat sodium (DSTAT, CX-01) is a low anticoagulant heparin with multiple mechanisms of action, including inhibition of the CXCR4/CXCL12 axis, blocking HMGB1, and binding platelet factor 4 (PF-4). We conducted a pilot study adding DSTAT to azacitidine for patients with AML or MDS unresponsive to or relapsed after prior hypomethylating agent therapy, hypothesizing that DSTAT may improve response rates. Twenty patients were enrolled, with a median of 2 prior lines of therapy and 6 cycles of prior hypomethylating agents. Among fifteen patients evaluable for response, there was 1 complete remission, and 3 marrow complete remissions, for a response rate of 27 % among evaluable patients (20 % overall). Hematologic improvement was observed in 5 additional patients. The median overall survival for all enrolled patients was 205 days (95 % CI 119-302). While cytopenias and infections were common, these were not out of proportion to what would be expected in this population of patients undergoing treatment with azacitidine alone. In summary, this trial demonstrated the feasibility of combining DSTAT with azacitidine, with several responses observed, suggesting this combination warrants further study., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF