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Tumor Angiogenesis pp 1–19Cite as

The Value of Anti-Angiogenics in Multiple Myeloma Therapy

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Abstract

Bone marrow angiogenesis is a hallmark of multiple myeloma and an important component of the profound myeloma-induced changes of the microenvironment. Bone marrow angiogenesis evaluated histologically or via dynamic contrast-enhanced magnetic resonance imaging (dceMRI) is a prognostic marker for survival for multiple myeloma (MM) patients. Normal and malignant plasma cells express angiogenic factors including vascular endothelial growth factors (VEGF) and are able to induce angiogenesis. The constitutive expression of angiogenesis factors by plasma cell accumulation of malignant plasma cells and increasing hypoxia is considered as initial drivers for bone marrow angiogenesis and remodeling of the bone marrow microenvironment in myeloma. Bone marrow angiogenesis may then be further accelerated by sequential loss of angiogenic inhibitors and/or aberrant expression of angiogenic factors during disease progression. Several novel agents such as immunomodulatory drugs (IMiDs), proteasome inhibitors, and histone deacetylase (HDAC) inhibitors approved for myeloma exert anti-angiogenic activity. Several considerations are expected to further develop anti-angiogenic treatment concepts in multiple myeloma: angiogenesis dependency and the “critical” angiogenesis-related drivers may vary and are dependent on the stage of myeloma development from monoclonal gammopathy of unknown significance (MGUS) up to symptomatic and therapy-resistant MM. Promising new agents targeting bone marrow angiogenesis are currently evaluated in early clinical studies including inhibitors of the hepatocyte-growth-factor pathway. Achieving clinical relevant effects might require the combination of angiogenesis inhibitors as well as rational combination with standard of care treatments.

It is expected that additional compounds with the ability to inhibit pathological bone marrow angiogenesis will be integrated into the therapeutic armamentarium for multiple myeloma in the future.

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Acknowledgments

We thank Mrs. Katja Weisert for administrative assistance.

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Authors and Affiliations

  1. Department of Medicine V, University of Heidelberg, Heidelberg, Germany

    Thomas Moehler, Dirk Hose, Anja Seckinger & Hartmut Goldschmidt

  2. Quintiles IMS GmbH, Hugenottenalle 167, Neu-Isenburg, Germany

    Thomas Moehler

  3. Institute of Pathology, University Ulm, Ulm, Germany

    Mindaugas Andrulis

  4. National Center for Tumor Diseases, Heidelberg, Germany

    Hartmut Goldschmidt

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  1. Thomas Moehler
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  2. Dirk Hose
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  3. Mindaugas Andrulis
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  5. Hartmut Goldschmidt
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Correspondence to Thomas Moehler .

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  1. Tumor Biology Center, Freiburg, Baden-Württemberg, Germany

    Dieter Marmé

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Moehler, T., Hose, D., Andrulis, M., Seckinger, A., Goldschmidt, H. (2017). The Value of Anti-Angiogenics in Multiple Myeloma Therapy. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-31215-6_34-1

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