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  • Correspondence
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Effectiveness of azacitidine in higher-risk myelodysplastic syndromes

Leukemia volume 30, pages 1795–1796 (2016)Cite this article

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We recently demonstrated in a population-based study that azacitidine may exhibit a potential to prolong overall survival over best supportive care (BSC) among particular patients with higher-risk myelodysplastic syndromes (HR-MDS).1 Just prior to the publication of our study, Bernal et al.2 conducted a similar population-based study among patients with HR-MDS. However, in contrast to our findings,1 their population-based analysis demonstrated that azacitidine does not have a beneficial effect over BSC.2 We previously delineated potential reasons for differences in outcome between both studies, such as an increased number of azacitidine treatment cycles in our study as opposed to the study by Bernal et al. (median, 8.5 vs 6).1 In response to our encouraging findings,1 Bernal et al.2, 3 proposed in a Correspondence to Leukemia that we should perform our analyses in a similar manner as they performed in their study, namely by employing a time-dependent methodology. More specifically, azacitidine was utilized as a time-dependent covariate in that study, which means that all patients with HR-MDS started in the BSC group as from time of HR-MDS diagnosis, with no patients initially starting in the azacitidine group.2 Patients changed from the BSC group to the azacitidine group at the time when treatment with azacitidine was initiated in first-line.2 Thus, patients who did not receive azacitidine in first-line, whatever the reason, stayed in the BSC group. The readership of Leukemia should, however, be aware that although the time-dependent methodology is statistically sound, employing such methodology in the clinical context of our population-based study has its limits.1

In this Correspondence, we will bring forward several arguments that speak in favor of the time-dependent methodology in order to explain to the readership of Leukemia in which setting that methodology is more suitable to be utilized for comparative effectiveness research. Further, we will justify the statistical methodology applied in our previous study in light of its clinical context.

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References

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Acknowledgements

The Population-based Haematological Registry for Observational Studies is an initiative of the Dutch-Belgian Hemato-Oncology Group (HOVON), the Institute of Medical Technology Assessment (iMTA/BMG) at the Erasmus University Rotterdam and the Netherlands Comprehensive Cancer Organisation (IKNL).

Author contributions

YvN provided advice on statistical analyses; AGD wrote the manuscript; and all authors read, commented on and approved the final version of the manuscript.

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Author notes

  1. A A van de Loosdrecht and M Jongen-Lavrencic: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Hematology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands

    A G Dinmohamed & M Jongen-Lavrencic

  2. Clinical Trial Center, HOVON Data Center, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands

    Y van Norden

  3. Department of Hematology, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands

    A A van de Loosdrecht

Authors
  1. A G Dinmohamed
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  2. Y van Norden
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  3. A A van de Loosdrecht
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  4. M Jongen-Lavrencic
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Correspondence to M Jongen-Lavrencic.

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Dinmohamed, A., van Norden, Y., van de Loosdrecht, A. et al. Effectiveness of azacitidine in higher-risk myelodysplastic syndromes. Leukemia 30, 1795–1796 (2016). https://doi.org/10.1038/leu.2016.117

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