Noopur S. Raje, MD, a professor of medicine at Harvard Medical School and director of the Multiple Myeloma Program at Massachusetts General Hospital, discusses quadruplet therapies that have been examined in multiple myeloma.

Three-drug combinations have been accepted as a standard of care in the up-front and relapsed settings for multiple myeloma, says Raje. The questions that arise now is: Can the field do better, and can quadruplets therapies be used? Typically a quadruplet regimen would be comprised of a 3-drug backbone with the addition of a monoclonal antibody. That is where the quadruplet regimen of carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) plus isatuximab (Sarclisa) comes into play, notes Raje. The quadruplet was examined in the phase 2 GMMG-CONCEPT trial and results showed an 100% overall response rate, with a very high proportion of patients achieving minimal residual disease (MRD) negativity. Other trials are ongoing, a handful of which have already been presented.

For example, in 2019, data from the phase 3 CASSIOPEIA trial with bortezomib, thalidomide (Thalomid), and dexamethasone (VTd) plus daratumumab (Darzalex) were reported, adds Raje. VTd was used in the trial because it is the standard of care in Europe, as lenalidomide was not yet approved there. Again, very high response rates and MRD negativity were reported with this regimen.

The depth of remission or response is very clear with these 4-drug combinations. Similarly, in the United States, the phase 2 GRIFFIN trial evaluated bortezomib, lenalidomide, and dexamethasone plus daratumumab. These data were presented by Peter Voorhees, MD, of Levine Cancer Institute, at the 2019 ASH Annual Meeting and showed a very high response rate with deep responses and MRD negativity, concludes Raje.