Analysis Explores Impact of Increased Point Mutations With High-Dose Melphalan in Myeloma

Mehmet K. Samur, PhD, senior research scientist, Dana-Farber Cancer Institute, discusses findings from an analysis evaluating high-dose melphalan (Evomela) followed by autologous stem cell transplant as treatment of patients with multiple myeloma compared with the standard of care treatment regimen lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVD) alone.

DNA sequencing data were collected from a total of 25 patients at the time of diagnosis and relapse. To compare this compilation, Samur says they also collected data from 43 patients with IFM/DCFI 2009 who only received RVD, both at diagnosis and relapse. The genomic alterations were compared at diagnosis and relapse among those injected with high-dose melphalan and RVD versus those treated with only RVD.

Patients who received a higher dose of melphalan in combination with RVD following by transplant accumulated more point mutations, Samur says, and to be precise, these patients accumulated around 10,000 new mutations between diagnosis and relapse at 5 years. For patients who received RVD alone, there were about 4500 new point mutations.

This study showed that treating patients with a high-dose regimen of melphalan increases the mutational load by about 2.9-fold at the time of relapse. These findings tell us a couple of things, Samur explains.