Panminerva medica
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While the outcome of patients with multiple myeloma has significantly improved over the last two decades, the disease remains incurable for the majority of patients. With the advent of novel agents, there has been a shift towards prolonged therapy as opposed to fixed-duration therapy, aimed at improving progression-free survival and overall survival. Evidence favoring continuous therapy has emerged over the last 2 decades and in the context of maintenance after proteasome inhibitor plus immunomodulatory drug induction followed by high dose melphalan and stem cell transplantation, this leads to >80% overall survival at 5 years. ⋯ As the survival improves, it is crucial to identify patients who are projected to have better survival and spare them toxicities arising from indefinite maintenance therapy. The role of minimal residual disease in this context is being investigated in numerous clinical trials and in the next few years the goal should be to use this in a rational way to achieve the ability to identify patients who would require continuation or escalation of therapy to improve their projected survival as well as to identify the group of patients in whom maintenance therapy could perhaps be time-limited without compromising their survival. Here we review the evidence for maintenance therapy from the key trials in the past years, present an overview of the current landscape and our perspective of maintenance therapy in the future.
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Proteasome inhibitors (PIs) represent a recently developed drug class that inhibit the ubiquitin-proteasome system, thus interfering with the intracellular machinery who has the duty of misfolded proteins disposal. Myeloma plasma cells are structurally aimed at the production of large quantities of immunoglobulins. This explains their vulnerability to any perturbation of intracellular protein homeostasis. ⋯ PIs are frequently used in doublets and triplets. Also, they can be associated with anti-CD38 monoclonal antibodies. This review summarizes the principal biological and clinical features of PIs in the MM treatment.