Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial

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This prospective phase II study evaluated the efficacy of azacitidine (Aza) + erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo + granulocyte colony stimulation factors for 48 weeks and a transfusion need of ≥ 4 units over 8 weeks were included. Aza 75mgm -2 d-1, 5/28 days, was given for six cycles; non-responding patients received another three cycles combined with Epo 60 000 units per week. Primary end point was transfusion independence (TI). All patients underwent targeted mutational screen for 42 candidate genes. Thirty enrolled patients received ≥ one cycle of Aza. Ten patients discontinued the study early, 7 due to adverse events including 2 deaths. Thirty-eight serious adverse events were reported, the most common being infection. Five patients achieved TI after six cycles and one after Aza + Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n = 3) and DNMT3A (n = 4) were only observed in nonresponders. We conclude that Aza can induce TI in severely anemic MDS patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations.


  • M. Tobiasson
  • I. Dybedahl
  • M. S. Holm
  • M. Karimi
  • L. Brandefors
  • H. Garelius
  • M. Grövdal
  • I. Högh-Dufva
  • K. Grønbæk
  • M. Jansson
  • C. Marcher
  • L. Nilsson
  • A. O. Kittang
  • A. Porwit
  • L. Saft
  • L. Möllgård
  • E. Hellström-Lindberg
Externa organisationer
  • Karolinska University Hospital
  • Norwegian Radium Hospital
  • Aarhus University Hospital
  • Karolinska Institute
  • Sunderby Hospital
  • Sahlgrenska University Hospital
  • Herlev Hospital
  • Copenhagen University Hospital
  • Odense University Hospital
  • University of Bergen
  • Skåne University Hospital

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Hematologi
  • Cancer och onkologi
TidskriftBlood Cancer Journal
StatusPublished - 2014 mar 7
Peer review utfördJa
Externt publiceradJa