Neutral tumor evolution in myeloma is associated with poor prognosis

Blood. 2017 Oct 5;130(14):1639-1643. doi: 10.1182/blood-2016-11-750612. Epub 2017 Aug 21.


Recent studies suggest that the evolutionary history of a cancer is important in forecasting clinical outlook. To gain insight into the clonal dynamics of multiple myeloma (MM) and its possible influence on patient outcomes, we analyzed whole exome sequencing tumor data for 333 patients from Myeloma XI, a UK phase 3 trial and 434 patients from the CoMMpass study, all of which had received immunomodulatory drug (IMiD) therapy. By analyzing mutant allele frequency distributions in tumors, we found that 17% to 20% of MM is under neutral evolutionary dynamics. These tumors are associated with poorer patient survival in nonintensively treated patients, which is consistent with the reduced therapeutic efficacy of microenvironment-modulating IMiDs. Our findings provide evidence that knowledge of the evolutionary history of MM has relevance for predicting patient outcomes and personalizing therapy.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Exome / drug effects
  • Female
  • Gene Frequency*
  • Genetic Drift
  • Humans
  • Immunologic Factors / therapeutic use*
  • Immunosuppressive Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Lenalidomide
  • Male
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / pathology
  • Mutation*
  • Prognosis
  • Thalidomide / analogs & derivatives*
  • Thalidomide / therapeutic use*
  • Tumor Microenvironment / drug effects


  • Immunologic Factors
  • Immunosuppressive Agents
  • Thalidomide
  • Lenalidomide