Risk and Response-Adapted Treatment in Multiple Myeloma

SIMPLE SUMMARY: Therapeutic strategies in multiple myeloma have been adapted only to age and comorbidities for a long time. Given the currently available therapeutic and technologic arsenal, the time may have come to refine this adaptation. First, high-risk patients should benefit from the most intensive and efficient combinations from diagnosis. Here, we review these different strategies and how to define and identify high-risk myeloma patients in current clinical practice. In addition, the advent of technologies detecting minimal residual disease gives us this opportunity to define the quality of response to treatment with an unpreceded sensitivity and adapt treatment accordingly. Finally, even if molecular targeting is still nascent in myeloma, some molecular features are interesting to detect at relapse to determine optimal salvage treatments. ABSTRACT: Myeloma therapeutic strategies have been adapted to patients’ age and comorbidities for a long time. However, although cytogenetics and clinical presentations (plasmablastic cytology; extramedullary disease) are major prognostic factors, until recently, all patients received the same treatment whatever their initial risk. No strong evidence allows us to use a personalized treatment according to one cytogenetic abnormality in newly diagnosed myeloma. Retrospective studies showed a benefit of a double autologous transplant in high-risk cytogenetics according to the International Myeloma Working Group definition (t(4;14), t(14;16) or del(17p)). Moreover, this definition has to be updated since other independent abnormalities, namely gain 1q, del(1p32), and trisomies 5 or 21, as well as TP53 mutations, are also prognostic. Another very strong predictive tool is the response to treatment assessed by the evaluation of minimal residual disease (MRD). We are convinced that the time has come to use it to adapt the strategy to a dynamic risk. Many trials are ongoing to answer many questions: when and how should we adapt the therapy, its intensity and duration. Nevertheless, we also have to take into account the clinical outcome for one patient, especially adverse events affecting his or her quality of life and his or her preferences for continuous/fixed duration treatment.