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Increasing recognition and emerging therapies argue for dedicated clinical trials in chronic myelomonocytic leukemia

Leukemia volume 35, pages 2739–2751 (2021)Cite this article

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Abstract

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). Median overall survival of this aggressive myeloid malignancy is only 2–3 years, with a 15–30% risk of acute leukemic transformation. The paucity of clinical trials specifically designed for CMML has made therapeutic management of CMML patients challenging. As a result, treatment paradigms for CMML patients are largely borrowed from MDS and MPN. The standard of care still relies on hydroxyurea, hypomethylating agents (HMA), and allogeneic stem cell transplantation, this latter option remaining the only potentially curative therapy. To date, approved drugs for CMML treatment are HMA, including azacitidine, decitabine, and more recently the oral combination of decitabine and cedazuridine. However, HMA treatment does not meaningfully alter the natural course of this disease. New treatment approaches for improving CMML-associated cytopenias or targeting the CMML malignant clone are emerging. More than 25 therapeutic agents are currently being evaluated in phase 1 or phase 2 clinical trials for CMML and other myeloid malignancies, often in combination with a HMA backbone. Several novel agents, such as sotatercept, ruxolitinib, lenzilumab, and tagraxofusp have shown promising clinical efficacy in CMML. Current evidence supports the idea that effective treatment in CMML will likely require combination therapy targeting multiple pathways, which emphasizes the need for additional new therapeutic options. This review focuses on recent therapeutic advances and innovative treatment strategies in CMML, including global and molecularly targeted approaches. We also discuss what may help to make progress in the design of rationally derived and disease-modifying therapies for CMML.

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Fig. 1: Treatment goals for CMML according to the myelodysplastic or myeloproliferative disease subtype.
Fig. 2: Therapeutic strategies for CMML patients.
Fig. 3: Targeting cell-autonomous mechanisms in CMML.
Fig. 4: Targeting non-cell autonomous mechanisms in CMML.

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  1. INSERM U1287, Gustave Roussy Cancer Campus, Villejuif, France

    Aline Renneville & Eric Solary

  2. Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    Mrinal M. Patnaik

  3. Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL, USA

    Onyee Chan & Eric Padron

  4. Faculty of Medicine, Université Paris-Sud, Le Kremlin-Bicêtre, France

    Eric Solary

  5. Department of Hematology, Gustave Roussy Cancer Campus, Villejuif, France

    Eric Solary

Authors
  1. Aline Renneville
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  2. Mrinal M. Patnaik
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  3. Onyee Chan
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  4. Eric Padron
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  5. Eric Solary
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Contributions

AR wrote the original draft and made figures. MMP, OC, EP, and ES revised the manuscript. ES supervised the work.

Corresponding author

Correspondence to Eric Solary.

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Competing interests

ES group was supported by research grants from Stemline and from Servier laboratories. EP has research funding from Incyte, Kura, and BMS. EP has received honorarium from Novartis, Taiho, Stemline, and Blueprint medicines.

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Renneville, A., Patnaik, M.M., Chan, O. et al. Increasing recognition and emerging therapies argue for dedicated clinical trials in chronic myelomonocytic leukemia. Leukemia 35, 2739–2751 (2021). https://doi.org/10.1038/s41375-021-01330-1

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  • DOI: https://doi.org/10.1038/s41375-021-01330-1

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