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

Leukemia & lymphoma 2021 Jun

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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.

Citation

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. A phase I trial evaluating the effects of plerixafor, G-CSF, and azacitidine for the treatment of myelodysplastic syndromes. Leukemia & lymphoma. 2021 Jun;62(6):1441-1449