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Achievement of a negative minimal residual disease state after hypomethylating agent therapy in older patients with AML reduces the risk of relapse

Leukemia volume 32, pages 241–244 (2018)Cite this article

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Minimal residual disease (MRD) is a powerful risk-stratification tool for the assessment of effectiveness of intensive induction chemotherapy in acute myeloid leukemia (AML).1, 2 Hypomethylating agents (HMAs) differ from conventional chemotherapy approaches in their mechanisms of action and dynamics of response.3, 4 In addition, the survival benefit with HMAs is not limited to patients attaining morphologic complete remission.5, 6 In keeping with this, whether HMA response should be measured in terms of MRD clearance may be viewed with skepticism. However, addition of novel targeted agents to HMAs in ongoing clinical trials has led to higher rates of morphological complete remission (CR) that are achieved more rapidly than with HMAs alone and has raised interest in the ability of such combinations to eradicate MRD. The clinical relevance of MRD monitoring in older patients with AML treated with HMAs has not been extensively evaluated before. In this report, we examine the prognostic value of MRD detection by multi-color flow cytometry (MFC) in a cohort of older AML patients treated with HMAs.

From February 2012 to November 2016, 194 patients, aged 60 years or older, with newly diagnosed AML were treated with azacitidine, decitabine or guadecitabine, on and off prospective clinical trials. Among them, 116 had flow MRD analysis performed on the bone marrow specimens obtained at the time of assessment of response or thereafter. Among these, 69 (59%) patients had achieved either a morphologic CR or CR with incomplete recovery of platelets (CRp) or counts (CRi), and 61 (53%) had evaluable MRD data (Supplementary Figure S1). All clinical trials as well the current study were approved by the institutional review board and conducted in accordance to the Declaration of Helsinki.

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Acknowledgements

We thank Mary Akosile and Graciela M Nogueras Gonzalez for providing valuable statistical input in the construction of data and performing statistical analysis. This study was supported by University of Texas MD Anderson Cancer Center Support Grant (P30 CA16672) and by the Leukemia SPORE Grant (P50 CA100632).

Author contributions

FR and PB provided conception and design of the study, collection, analysis and interpretation of data, provided patient data for study, writing and revising the manuscript and final review and approval of the manuscript. SP and MB provided collection and analysis of data. HK, JJ, GGM, JC, TK, GB, CD, EJ, PB, ND, MY, KN, YA, MK and NP provided data for the study, and review and approval of the manuscript.

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Authors and Affiliations

  1. Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    P Boddu, H Kantarjian, G Borthakur, T Kadia, N Daver, Y Alvarado, N Pemmaraju, P Bose, K Naqvi, M Yilmaz, S Pierce, M Brandt, C D DiNardo, E J Jabbour, M Konopleva, G Garcia-Manero, J Cortes & F Ravandi

  2. Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    J Jorgensen

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  1. P Boddu
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Corresponding author

Correspondence to F Ravandi.

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Boddu, P., Jorgensen, J., Kantarjian, H. et al. Achievement of a negative minimal residual disease state after hypomethylating agent therapy in older patients with AML reduces the risk of relapse. Leukemia 32, 241–244 (2018). https://doi.org/10.1038/leu.2017.285

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