New Drugs and New Strategies for the Treatment of Multiple Myeloma Patients

Multiple myeloma still remains an incurable disease with a high incidence rate in the elderly. Near the old active classes of drugs: alkylators (e.g., melphalan and cyclophosphamide), corticosteroids (e.g., prednisone and dexamethasone), and anthracyclines (e.g., doxorubicin), new drug formulations (e.g., liposomal doxorubicin) and new active classes of drugs such as proteasome inhibitors (e.g., bortezomib) and immunomodulatory drugs (e.g., thalidomide and lenalidomide) have been introduced in myeloma therapy. The high heterogeneity of this disease leads to large differences in clinical responses to treatments. High response rates and good quality responses with a long-term disease control can be observed with the introduction of new drugs. Changes in treatment strategies due to the introduction of novel drugs have been able to improve significantly the quality of responses. In fact, if in the past, Complete Remission (CR) in MM was rare to achieve, while the introduction of new treatments have increased the rate in younger patients as well as in non-transplant setting. CR represents a surrogated marker of long survival. It correlates with the long-term Progression-Free Survival (PFS) and Overall Survival (OS). Achieving CR and sustaining CR within a 3-year landmark from the treatment initiation is associated with highly superior survival. Actually, we agree that ―The more profound the remission, the longer the duration of response‖. Moreover, the interactions between tumor cells and their bone marrow microenvironment play a pivotal role in myeloma progression, inducing also drug resistance. This knowledge has improved treatment options leading to the approval of new drugs which target the malignant cell itself and also its microenvironment. These agents are in preclinical/early clinical evaluation and they appear to further improve disease control but their use is still not approved outside of clinical trials.