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. 2014 Mar 7;4(3):e189.
doi: 10.1038/bcj.2014.8.

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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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

M Tobiasson et al. Blood Cancer J. .
Free PMC article


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 >8 weeks and a transfusion need of 4 units over 8 weeks were included. Aza 75 mg m(-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 non-responders. 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.


Figure 1
Figure 1
Illustration of mutational and cytogenetic status for included patients.
Figure 2
Figure 2
(a) Outcome after azacitidine as monotherapy and the combined treatment of azacitidine and erythropoietin (Epo). Response is defined as transfusion independence. (b) Duration of response. (c) Overall survival. (d) Leukemic transformation.

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    1. Jadersten M, Montgomery SM, Dybedal I, Porwit-MacDonald A, Hellstrom-Lindberg E. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood. 2005;106:803–811. - PubMed
    1. Park S, Grabar S, Kelaidi C, Beyne-Rauzy O, Picard F, Bardet V, et al. Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience BloodUnited States2008111574–582. - PubMed
    1. Greenberg PL, Sun Z, Miller KB, Bennett JM, Tallman MS, Dewald G, et al. Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996) Blood. 2009;114:2393–2400. - PMC - PubMed
    1. Kelaidi C, Park S, Sapena R, Beyne-Rauzy O, Coiteux V, Vey N, et al. Long-term outcome of anemic lower-risk myelodysplastic syndromes without 5q deletion refractory to or relapsing after erythropoiesis-stimulating agents. Leukemia. 2013;27:1283–1290. - PubMed
    1. Hellstrom-Lindberg E, Negrin R, Stein R, Krantz S, Lindberg G, Vardiman J, et al. Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br J Haematol. 1997;99:344–351. - PubMed