Importance of achieving a complete response in multiple myeloma, and the impact of novel agents

Abstract

The goal of treatment for multiple myeloma (MM) is to improve patients' long-term outcomes. One important factor that has been associated with prolonged progression-free and overall survival is the quality of response to treatment, particularly achievement of a complete response (CR). There is extensive evidence from clinical studies in the transplant setting in first-line MM demonstrating that CR or maximal response post-transplant is significantly associated with prolonged progression-free and overall survival, with some studies demonstrating a similar association with postinduction response. Supportive evidence is also available from studies in the nontransplant and relapsed settings. With the introduction of bortezomib, thalidomide, and lenalidomide, higher rates of CR are being achieved in both first-line and relapsed MM compared with previous chemotherapeutic approaches, thereby potentially improving long-term outcomes. While standard CR by established response criteria has been shown to have differential prognostic impact compared with lesser responses, increasingly sensitive analytic techniques are now being explored to define more stringent degrees of CR or elimination of minimal residual disease (MRD), including multiparameter flow cytometry and polymerase chain reaction. Demonstrating eradication of MRD by these techniques has already been shown to predict for improved outcomes. Here, we review the prognostic significance of achieving CR in MM and highlight the importance of CR as an increasingly realizable goal at all stages of treatment. We discuss clinical management issues and provide recommendations relevant to practicing oncologists, such as the routine use of sensitive techniques for assessment of disease status to inform evidence-based decisions on optimal patient management.