A phase I trial evaluating the effects of plerixafor, G-CSF, and azacitidine for the treatment of myelodysplastic syndromes
Year: 2021
Type: article
Study design: Clinical Trial
Abstract: Interactions between the bone marrow microenvironment and MDS tumor clones play a role in pathogenesis and response to treatment. We hypothesized G-CSF and plerixafor may enhance sensitivity to azacitidine in MDS. Twenty-eight patients with MDS were treated with plerixafor, G-CSF and azacitidine with a standard 3 + 3 design. Subjects received G-CSF 10 mcg/kg D1–D8, plerixafor D4–D8, and azacitidine 75 mg/m2 D4–D8, but the trial was amended to reduce G-CSF dose to 5 mcg/kg for 5 days after 2 patients had significant leukocytosis. Plerixafor was dose escalated to 560 mcg/kg/day without dose limiting toxicity. Two complete responses and 6 marrow responses were seen for an overall response rate (ORR) of 36% in evaluable patients, and ORR of 53% in patients receiving the triplet. Evidence of mobilization correlated with a higher ORR, 60% vs. 17%. Plerixafor, G-CSF and azacitidine appears tolerable when given over 5 days and has encouraging response rates.KEY POINTSPlerixafor and G-CSF can be safely combined with azacitidine for 5 days in patients with MDS.The overall response rate of 53% for evaluable patients with this regimen is higher than expected and more responses were seen in patients with blast mobilization.
Authors: Eric Huselton, Michael P. Rettig, Theresa Fletcher, Julie Ritchey, Leah Gehrs, Kyle McFarland, Stephanie Christ, William C. Eades, Kathryn Trinkaus, Rizwan Romee, Shashikant Kulkarni, Armin Ghobadi, Camille Abboud, Amanda F. Cashen, Keith Stockerl-Goldstein, Geoffrey L. Uy, Ravi Vij, Peter Westervelt, John F. DiPersio, Mark A. Schroeder
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: OPTIMIZING ALLOGENEIC TRANSPLANTATION USING CXCR4 BLOCKADE, G2029646967, G2120055183, TARGETING THE CXCR4-SDF1 AXIS AS THERAPY FOR RELAPSED/REFRACTORY AML, CLINICAL HEMATOLOGY RESEARCH CAREER DEVELOPMENT PROGRAM AT WASHINGTON UNIVERSITY, G5541092659, G6102789425, Washington University Institute of Clinical and Translational Sciences, TARGETING AML-STROMAL INTERACTIONS, G8753643024, G8914033231, Washington University Institute of Clinical and Translational Sciences, Optimizing Hematopoietic Stem Cell Transplantation For The Treatment Of Hematological Malignancies, Cancer Center Support Grant, Washington University Paul Calabresi K12 Career Development Award for Clinical Oncology
OpenAlex ID: W3123979395