**5. Conclusions**

Despite the good results obtained in the last decades, MM remains an incurable malignancy, indicating that our knowledge on the mechanisms responsible for disease progression and drug resistance is still not completely clear. The goal obtained with the introduction of the new target drugs for MM therapy is the improvement of the outcome of MM patients in term of progression-free and overall survival. The simultaneous block of plasma cell proliferation and survival, plasma cells/BM stromal cells interaction, and BM stromal cells activity by the novel agents help us to get these results. In fact, the BM microenvironment plays a crucial role in the pathophysiology of MM. An active crosstalk between MM plasma cells and stromal cells in the BM of myeloma patients is constantly working. It represents a hallmark of active MM favoring survival, proliferation, and migration of plasma cells, and modulates neovessel formation by mean angiogenesis favoring the disease progression. The crosstalk between MM plasma cells and BM microenvironment is not only responsible for drug resistance of plasma cells but also of endothelial cells and other cells composing the microenvironment. The better understanding of the biological mechanisms controlling the interactions between MM cells and BM stromal cells remain fundamental for our knowledge about disease progression and for developing novel drugs targeting these processes.

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