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Editorials
Clonal evolution in myeloma: a narrow road to remission
Cornelius C. Miething
Universitätsklinikum Freiburg, Klinik für Innere Medizin I, Freiburg, Germany E-mail: CORNELIUS C. MIETHING - cornelius.miething@uniklinik-freiburg.de
doi:10.3324/haematol.2019.220152
Over the last twenty years, a wave of new therapies has made a profound impact on the treatment and prognosis of multiple myeloma. The advent of pro- teasome inhibitors and thalidomide and its successors have increased the response rates to first-line therapy in myelo- ma to more than 90%, with a median time to progression of over 45 months.1 This development continues, with fur- ther improvements expected through up and coming agents, such as second- and third-generation proteasome inhibitors and immunomodulatory drugs (IMID), novel
antibodies, and targeted immunotherapeutics.2 Furthermore, new approaches to measuring minimal resid- ual disease (MRD) have demonstrated a clear connection between progression-free survival (PFS)/overall survival (OS) and the achievement of MRD negativity as deter- mined by high sensitivity flow cytometry or next-genera- tion sequencing (NGS),3,4 opening up new approaches for prognostic and therapeutic stratification. Interestingly, the impact of MRD negativity also holds true for high-risk myeloma patients, who show an improved prognosis if
Figure 1. Clonal evolution during therapy (adapted from Jones et al.8). Myeloma patients achieving a complete or very good partial remission are generally character- ized by a branching evolution of the clonal architecture upon relapse (top), with fre- quent loss of clones present at diagnosis and concomitant gain of clones carrying additional new mutations. In contrast, myeloma patients with a partial response to the initial therapy mostly showed stable clonal patterns without evidence of signifi- cant clonal selection (bottom).
haematologica | 2019; 104(7)