Novel agents and the paradigm of continuous treatment in multiple myeloma

Abstract

Multiple myeloma (MM) is a hematologic malignancy that primarily affects those aged >65 years [1]. The disease remains incurable despite major advances in treatment, such as highdose therapy followed by autologous stem-cell transplantation (ASCT), and the availability of novel anti-myeloma agents such as thalidomide, lenalidomide, and bortezomib. Introduction of these novel agents has greatly extended survival times in MM patients [2,3]; however, long-term remissions are rare and outcomes in elderly transplant-ineligible patients in particular remain poor [4]. In most patients, MM is characterized by a progressive pattern of treatment and relapse that leads to the development of an advanced, treatment-refractory disease. Most patients with MM eventually relapse due to the existence of clonogenic, residual MM cells, which persist even in those who clinically show a complete response to treatment. Therefore, a focus of current clinical research is the identification of treatment approaches that are able to suppress residual MM cells and delay progression of the disease. Treatment regimens based on the novel agents thalidomide, lenalidomide, and bortezomib are effective in patients with newly diagnosed MM [5–8], and in those with relapsed/refractory disease [9–12]. However, the optimal duration of treatment in MM patients has not been defined and the duration of treatment is individualized. In this context, continuous therapy with novel agents is being evaluated as a strategy for longterm disease control across lines of treatment. The concept being evaluated is whether continuous treatment with a novel agent, either alone or in combination with other treatments, can lead to long-term clinical remissions. The recently reported results of the MM-015 trial [7], which evaluated continuous lenalidomide therapy in elderly patients with newly diagnosed MM, have sparked new interest in continuous therapy and raised several important practical questions regarding its integration into current practice. To address these issues, I developed the concept of a journal supplement devoted specifically to the topic of continuous therapy and invited some of my distinguished colleagues to contribute articles to the supplement. A journal supplement seemed to be an appropriate medium to consolidate the available evidence, address a wide range of issues related to the topic, and provide different perspectives from experts in the field of MM therapy.