Dr. Shah on Daratumumab-Based Regimens in Frontline Multiple Myeloma

Nina Shah, MD, associate professor of medicine at the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, discusses daratumumab (Darzalex)-based regimens in the frontline treatment of patients with multiple myeloma.

Daratumumab has become an important component of triplet and quadruplet regimens in the frontline treatment of patients with multiple myeloma, says Shah. In the phase III ALCYONE trial, the addition of daratumumab to bortezomib (Velcade), melphalan, and prednisone (VMP) was superior to VMP alone in transplant-ineligible patients. Since melphalan is not widely used in the United States, the regimen isn’t as relevant to current practice, adds Shah.

However, results from the phase III MAIA trial showed that the addition of daratumumab to lenalidomide (Revlimid) and dexamethasone (Rd) is superior to Rd alone in transplant-ineligible patients. Accordingly, the triplet regimen was approved for use as frontline therapy in this patient population.

Furthermore, the phase III CASSIOPEIA trial demonstrated an improvement in progression survival (PFS) with the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (VTd) versus VTd alone in transplant-eligible patients following induction therapy and transplant. As a result, daratumumab was approved for use in the frontline setting for transplant-eligible patients. However, thalidomide is not commonly used in the United States, says Shah.

Finally, the phase II GRIFFIN study evaluated the addition of daratumumab to lenalidomide, bortezomib, and dexamethasone (D-RVd) versus RVd alone. Preliminary data showed a deeper response with the quadruplet, which translated to a higher rate of stringent complete responses and minimal residual disease negativity compared with the triplet. Although the PFS data are immature, D-RVd is beginning to be adopted into clinical practice, says Shah. Whether carfilzomib (Kyprolis) should replace bortezomib remains an area of active consideration.