Panminerva medica
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Over the last two decades, the outcomes of patients with multiple myeloma (MM), a malignant plasma cells dyscrasia, have dramatically improved. The development and the introduction of the immunomodulatory drugs (IMiDs) which include thalidomide, lenalidomide, and pomalidomide, have contributed significantly to these improvements. ⋯ Here the mechanisms of action, the clinical efficacy and the management of side effects are reviewed as well as the new classes of cereblon E3 ligase modulator (CELMoD) and their promising clinical data are described.
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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.