New Compass Findings

This month in CoMMpass Study publications brings a new paper from lead author Dr. Michael Chapman of the University of Cambridge, who was also an author on the 2 original papers reporting on the sequencing of the myeloma genome, work that was sponsored and directed by the MMRF.

Articles:

  1. Initial genome sequencing and analysis of multiple myeloma
  2. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy

The recent paper, published in the journal Blood, discusses how Chapman and colleagues used sequencing data from the CoMMpass study to help identify a set of markers that can predict how well newly diagnosed patients will respond to Revlimid- or Velcade-based therapies.  

The authors looked at 44 patient outcomes in a European study called PADIMAC , where newly diagnosed myeloma patients were treated with Velcade, Adriamycin, and Dexamethasone. They looked at the RNA sequences in PADIMAC patients who had good outcomes on the therapy, and those who had worse outcomes, and were able to identify 7 genes which, when present, could predict how well patients responded to Velcade. They then tested this signature on patients in a separate trial to see if it could predict which patients would respond well to Velcade-dex vs. Revlimid-dex therapies, and found that the 7 gene signature could indeed predict which patients would respond best to Velcade-dex.

Finally, the authors looked at outcomes for patients in the CoMMpass study. They found that patients who were treated “correctly”  in CoMMpass, according to their 7-gene signature, had better progression free survival than those who were treated “incorrectly”. In fact, those patients who were treated with the Velcade-dex doublet therapy that was predicted to work for them based on the 7-gene marker actually did just as well as patients who were on a triplet Velcade-Revlimid-dex regimen.

This is important work for several reasons:

  • This test might help doctors determine which regimen will be most effective in newly diagnosed myeloma patients
  • The test only has 7 genes, and might be easily translated to the clinic for use with all newly diagnosed patients
  • The fact that the signature may predict which patients would do just as well on a doublet therapy vs a triplet therapy is important information for patients who may not be able to tolerate a triplet regimen

The results in this paper show that treatment outcomes in myeloma may be improved by rational selection of drugs based on the biology, or genome sequence, of their specific tumor. This is the promise of precision medicine. The decision to use a doublet vs. a triplet regimen could be key in improving both the safety and cost-effectiveness of these drug regimens. If these results are validated by further studies in the clinic, they will provide further evidence of the utility of precision medicine in defining appropriate treatments for myeloma patients at each stage of their disease.