Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma

P. Leif Bergsagel, María-Victoria Mateos, Norma C. Gutierrez, S. Vincent Rajkumar and Jesús F. San Miguel


Multiple myeloma (MM) is a heterogeneous disease with certain genetic features (e.g., t(4;14), del17p) associated with worse outcome. The introduction of thalidomide, lenalidomide and bortezomib has dramatically improved the outlook for patients with MM, but their relative benefit (or harm) for different genetic patient subgroups remains unclear. Unfortunately, the small numbers of patients in each subgroup frequently limits the analysis of high-risk patients enrolled in clinical trials. Strategies that result in survival of high-risk genetic subgroups approximating that of patients lacking high-risk features are said to overcome the poor prognostic impact of these high-risk features. This outcome has been difficult to achieve, and studies in this regard have so far been limited by inadequate sample size. In contrast, strategies that compare the survival of high-risk genetic subgroups randomized to different treatment arms can identify approaches that improve survival. This type of analysis is clinically useful, even if the absolute gains do not improve outcomes to levels seen in patients without high-risk cytogenetics. Reviewing available data in high-risk MM from this perspective, it appears that bortezomib has frequently been associated with improved survival, while thalidomide maintenance has sometimes been associated with a shorter survival.

  • Submitted May 24, 2012.
  • Accepted November 6, 2012.