Heterogeneity of outcome with single-agent carfilzomib: all relapsed/refractory myelomas are not created equal

Abstract

Since the year 2000, there has been a continued improvement in survival outcomes for multiple myeloma (MM) patients,1 attributable to the clinical development and inclusion of novel agents in upfront therapy, and improvement in high-dose therapy administration.2 There has been a growing body of literature furthering the biological understanding of the disease. There is a clear recognition of both inter-patient and intra-patient genomic heterogeneity in multiple myeloma,3 although the academic community is still trying to comprehend specific phenotypic presentations such as primary plasma cell leukemia4 and extramedullary disease.5 Even with effective upfront therapeutic strategies, which seemingly help a greater proportion of MM patients achieve a ‘complete’ remission by biochemical and pathology criteria, relapses do occur sooner or later that require subsequent lines of therapy. There is a growing list of classes of novel agents that are disease-relevant and showing promise in early clinical investigations in the relapsed/refractory MM (RRMM) setting. These classes include histone deacytelase inhibitors, heat-shock protein inhibitors, kinesin spindle protein inhibitors, immune-therapeutics and ubiquitin-proteasome pathway targeting agents.6 We have witnessed the Food and Drug Administration approval of two novel agents in the past 12 months, namely carfilzomib and pomalidomide, in the RRMM setting. It is highly likely that several novel agents will acquire Food and Drug Administration approval for RRMM over the next 5 years. The challenges in this setting would then be to determine which class of drugs may be more suitable for an individual patient, whether it would be better to sequence or combine different drug classes, and whether or not it would be possible to achieve ‘functional cure’ by making RRMM a chronic disease for most patients.