Relapsed/Refractory Multiple Myeloma: The Current State of Play

Abstract

Multiple myeloma (MM) usually responds to treatment but is incurable. The clinical course is characterised, in most patients, by a series of remissions and relapses. For younger patients, the initial treatment currently usually involves induction with the proteasome inhibitor bortezomib (BOR), alone or in combination, followed by an autologous stem cell transplant (ASCT). Usually only clinical relapses require treatment; the treatment plan should be individualised to take into account factors such as response to previous treatment, duration of the remission, adverse effects experienced, and available treatment options. Evidence suggests that many patients who have responded to BOR will respond to it again. Patients at first relapse should also be considered for a further ASCT or an allotransplant. Clinical studies have led to other drugs being approved for treatment of relapsed MM. These include lenalidomide (an immunomodulatory drug), carfilzomib (another proteasome inhibitor), pomalidomide (an immunomodulatory drug), and most recently panobinostat (a deacetylase inhibitor). The availability of these drugs greatly enhances the therapeutic options available to treat further relapses. Moreover, a bewildering array of other novel agents are at various stages in testing. They include other drugs from the classes already mentioned, as well as monoclonal antibodies, drugs acting on the cell cycle, kinase inhibitors, and signal transduction pathway inhibitors. It seems probable that the introduction of these agents in the coming years will further improve the survival of patients with MM, and may even lead to a cure.