A phase II, multicentre trial of decitabine in higher-risk chronic myelomonocytic leukemia

Valeria Santini ,Elisa Masiera ,Daniela Gioia ,Giuseppe Saglio ,Manuela Ceccarelli ,Emanuele Angelucci ,Francesco Onida ,Anna Maria Pelizzari ,Antonella Poloni ,Monia Lunghi ,María E Figueroa ,Daniela Cilloni ,Adelmo Terenzi ,Omar Abdel‐Wahab ,Carlo Finelli ,Gina Zini ,Dario Ferrero ,Alessandro Sanna ,Bernardino Allione ,Alessandro Levis

doi:10.1038/leu.2017.186

Abstract

Chronic myelomonocytic leukemia (CMML) is a complex clonal hematological disorder classified among myelodysplastic (MDS)/myeloproliferative neoplasms. Prognosis is poor and there is a lack of effective treatments. The hypomethylating agent decitabine has shown activity against MDS and elderly acute myeloid leukemia, but there is little data focusing specifically on its efficacy in CMML. In this prospective, phase 2 Italian study, CMML patients received intravenous decitabine 20 mg/m2 per day on Days 1–5 of a 28-day treatment cycle. Response was evaluated after four and six cycles; patients responding at the end of six cycles could continue treatment with decitabine. Forty-three patients were enrolled; >50% were high-risk according to four CMML-specific scoring systems. In the intent-to-treat population (n=42), the overall response rate after six cycles was 47.6%, with seven complete responses (16.6%), eight marrow responses (19%), one partial response (2.4%) and four hematological improvements (9.5%). After a median follow-up of 51.5 months (range: 44.4–57.2), median overall survival was 17 months, with responders having a significantly longer survival than non-responders (P=0.02). Grade 3/4 anemia, neutropenia and thrombocytopenia occurred in 28.6%, 50% and 38% of patients, respectively. Decitabine appears to be an effective and well-tolerated treatment for patients with high-risk CMML.

Highlights

IntroductionOrganization among myelodysplastic (MDS)/myeloproliferative neoplasms.[1] The 2016 revision to the World Health Organization classification of tumors of the hematopoietic and lymphoid tissues describes three categories of Chronic myelomonocytic leukemia (CMML) based on blast count:[2,3] CMML-0 (o2% peripheral blasts and o 5% bone marrow blasts), CMML-1 (2‒4% peripheral blasts and/or 5‒9% bone marrow blasts) and CMML-2 (5‒19% peripheral blasts, 10‒19% bone marrow blasts and/or presence of Auer rods)
Chronic myelomonocytic leukemia (CMML) is a complex clonal hematological disorder that is classified by the World HealthOrganization among myelodysplastic (MDS)/myeloproliferative neoplasms.[1]
The 2016 revision to the World Health Organization classification of tumors of the hematopoietic and lymphoid tissues describes three categories of CMML based on blast count:[2,3] CMML-0 (o2% peripheral blasts and o 5% bone marrow blasts), CMML-1 (2‒4% peripheral blasts and/or 5‒9% bone marrow blasts) and CMML-2 (5‒19% peripheral blasts, 10‒19% bone marrow blasts and/or presence of Auer rods)

Summary

Introduction

Organization among myelodysplastic (MDS)/myeloproliferative neoplasms.[1] The 2016 revision to the World Health Organization classification of tumors of the hematopoietic and lymphoid tissues describes three categories of CMML based on blast count:[2,3] CMML-0 (o2% peripheral blasts and o 5% bone marrow blasts), CMML-1 (2‒4% peripheral blasts and/or 5‒9% bone marrow blasts) and CMML-2 (5‒19% peripheral blasts, 10‒19% bone marrow blasts and/or presence of Auer rods). Before this revision, patients with o 2% peripheral blasts and o5% bone marrow blasts were included in the CMML-1 category.[4]. Newer prognostic models (such as the CMML-specific prognostic scoring system,[8,9] Groupe Francophone de Myelodysplasies (GFM) model[10] and the Mayo Molecular Model11) take cytogenetics and somatic mutations into account

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