Abstract
Over the last years, there has been great progress in the treatment of multiple myeloma with many new agents and combinations having been approved and being now routinely incorporated into treatment strategies. As a result, patients are experiencing benefits in terms of survival and better tolerance. However, the multitude of treatment options also presents a challenge to select the best options tailored to the specific patient situation. Lenalidomide is increasingly being used as part of frontline therapy in newly diagnosed multiple myeloma. This agent is typically administered until disease progression. It is currently unclear, how to best manage patients, who relapse while receiving lenalidomide as part of their frontline treatment. We conducted a review to summarize the available evidence in this setting. Our summary shows that there are very few data from current trials testing new combinations based on carfilzomib, pomalidomide, or daratumumab that address this specific patient population. Our review is aimed to summarize the available evidence to assist treatment decision making and to raise awareness of this lack of data to encourage further analyses and the incorporation of sequencing questions in future trial designs.
Highlights
The treatment of multiple myeloma (MM) has changed dramatically in the past decade with the introduction of new drugs into therapeutic strategies, both in the frontline and in the relapse settings
With the availability of at least 6 different classes of approved agents, i.e., alkylators, steroids, proteasome inhibitors (PIs), immunomodulatory agents (IMiDs), histone deacetylase inhibitors (DACIs) and monoclonal antibodies (MoAbs) that can be combined in doublet, triplet or even quadruplet regimens, and used together with or without high-dose therapy and autologous stem cell transplantation (ASCT), or in some cases as Correspondence: Philippe Moreau 1University Hospital Hotel-Dieu, Nantes, France 2Istituto Seragnoli, Bologna, Italy Full list of author information is available at the end of the article
Problematic is the lack of trials addressing important questions, such as the integration of the first salvage regimen into the assessment of front-line therapies in order to define optimal sequencing strategies and to evaluate progression-free survival 2 (PFS2) as an important end point in homogeneous patient populations
Summary
The treatment of multiple myeloma (MM) has changed dramatically in the past decade with the introduction of new drugs into therapeutic strategies, both in the frontline and in the relapse settings. The only information available is based on a sub-analysis, showing that patients refractory to lenalidomide, regardless of the number of prior lines of therapy, (DVd, n = 60; Vd, n = 81) achieved a significant PFS benefit with DVd versus Vd, with medians of 7.8 versus 4.9 months, respectively, not very different from the data reported in the ENDEAVOR study for a similar subgroup of patients[24].
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