A phase I trial evaluating the effects of plerixafor, G-CSF, and azacitidine for the treatment of myelodysplastic syndromes

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 POINTS Plerixafor 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.

Original languageEnglish
Pages (from-to)1441-1449
Number of pages9
JournalLeukemia and Lymphoma
Volume62
Issue number6
DOIs
StatePublished - 2021

Keywords

  • G-CSF
  • MDS
  • Plerixafor
  • azacitidine

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