Outcome of lower-risk patients with myelodysplastic syndromes without 5q deletion after failure of erythropoiesis-stimulating agents

Sophie Park, Jean François Hamel, Andrea Toma, Charikleia Kelaidi, Sylvain Thépot, Maria Diez Campelo, Valeria Santini, Mikkael A. Sekeres, Enrico Balleari, Jennifer Kaivers, Rosa Sapena, Katharina Götze, Catharina Müller-Thomas, Odile Beyne-Rauzy, Aspasia Stamatoullas, Ioannis Kotsianidis, Rami Komrokji, David P. Steensma, Jaime Fensterl, Gail J. RobozTeresa Bernal, Fernando Ramos, Marisa Calabuig, Agnès Guerci-Bresler, Dominique Bordessoule, Pascale Cony-Makhoul, Stéphane Cheze, Eric Wattel, Christian Rose, Norbert Vey, Daniela Gioia, Dario Ferrero, Gianluca Gaidano, Giovanni Cametti, Fabrizio Pane, Alessandro Sanna, Ulrich Germing, Guillermo F. Sanz, François Dreyfus, Pierre Fenaux

Research output: Contribution to journalArticle

Abstract

Purpose: Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Secondline treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods: We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results: Erythroid response to ESAs was 61.5%, and median response duration was 17 months. Of 1,147 patients experiencing ESA failure, 653 experienced primary failure and 494 experienced relapse after a response. Primary failure of ESAs was associated with a higher risk of acute myeloid leukemia (AML) progression, which did not translate into an OS difference. Of 450 patients (39%) who received second-line treatment, 194 received HMAs, 148 received LEN, and 108 received other treatments (MISC), whereas 697 received RBC transfusions only. Five-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for those receiving HMAs, LEN, and MISC, respectively (P =.05). Five-year OS for patients receiving HMA, LEN, and MISC was 36.5%, 41.7%, and 51%, respectively (P =.21). In a multivariable analysis adjusted for age, sex, revised International Prognostic Scoring System score, and progression at ESA failure, there was no significant OS difference among the three groups. Conclusion: In this large, multicenter, retrospective cohort of patients with non-del(5q) lower-risk MDS treated with ESAs, none of the most commonly used second-line treatments (HMA and LEN) significantly improved OS. Early failure of ESAs was associated with a higher risk of AML progression.

Original languageEnglish
Pages (from-to)1591-1597
Number of pages7
JournalJournal of Clinical Oncology
Volume35
Issue number14
DOIs
Publication statusPublished - May 10 2017

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Park, S., Hamel, J. F., Toma, A., Kelaidi, C., Thépot, S., Campelo, M. D., Santini, V., Sekeres, M. A., Balleari, E., Kaivers, J., Sapena, R., Götze, K., Müller-Thomas, C., Beyne-Rauzy, O., Stamatoullas, A., Kotsianidis, I., Komrokji, R., Steensma, D. P., Fensterl, J., ... Fenaux, P. (2017). Outcome of lower-risk patients with myelodysplastic syndromes without 5q deletion after failure of erythropoiesis-stimulating agents. Journal of Clinical Oncology, 35(14), 1591-1597. https://doi.org/10.1200/JCO.2016.71.3271