Blood Spotlight Pursuing the curative blueprint for early myeloma

The treatment of multiple myeloma (MM) has witnessed remarkable progress since the implementation of proteasome inhibitors and immunomodulatory agents. Combining these agents with highdose melphalan results in nonprogressive disease in a significant number of patients but is not universally tolerated. No integrated therapeutic strategy exists that reliably results in eradication of disease: a fact that earns MM the label of an incurable malignancy. The fundamental question regarding the curability of MM sparks much disagreement and controversy. Philosophical debates have scrutinized whether the goal of therapy should be an ardent pursuit of complete response (“curative” doctrine) or longitudinal management of a chronic disease that perpetually remits and relapses (“control” doctrine). At its core, the philosophical divide hinges on the efficacy and toxicity of the therapies used and requires careful reconsideration as agents evolve. Indeed, the inherent curability of MM remains the most profound unanswered fundamental question. The pursuit of a breakthrough curative blueprint for MM is a justifiable concept, and the necessary components require definition. Elements of both treatment doctrines are critical for a curative blueprint because combinations of highly active agents are required to achieve maximal eradication of both founder and minor subclones (“curative” doctrine), and diseasemodulation after initial therapywill likely be required to extend response duration (“control” doctrine). These hypotheses must be rigorously studied inwell-designed clinical trials prior to the widespread implementation of regimens without proven survival benefit. We propose a shift in research focus toward studying the effect of combination therapy delivered prior to overt organ dysfunction and advanced genomic complexity (ie, treatment of “early myeloma”) combined with highly sensitive methods of subclinical disease monitoring (Figure 1).