Integrating Agents in Relapsed/Refractory Multiple Myeloma

The PANORAMA-1 trial showed that patients who derived the most benefit from panobinostat had received two or more prior lines of therapy, including both a proteasome inhibitor and an IMiD. However, data from clinical trials suggest that panobinostat synergizes effectively with proteasome inhibitors as well as IMiDs, says Andrew Spencer, MD. To improve tolerability, Spencer uses weekly bortezomib administered subcutaneously in combination with panobinostat in the third-line setting, or uses a week-on/week-off schedule with the two agents.

Pomalidomide is a second-generation oral immunomodulatory agent (IMiD) approved in Europe in combination with low-dose dexamethasone for the treatment of relapsed and refractory multiple myeloma, says Maria-Victoria Mateos, MD, PhD. Patients who have had a long progression-free survival after prior lenalidomide-based therapy tend to benefit the most from pomalidomide-based therapy, says Jatin J. Shah, MD. Certain subsets of patients with high-risk disease also benefit from pomalidomide, adds Shah. Pomalidomide has shown activity in combination with cyclophosphamide and also with carfilzomib.

Carfilzomib is a second-generation proteasome inhibitor approved in the United States as a single agent for the treatment of patients who are relapsed and refractory to bortezomib and lenalidomide, says Mateos. Carfilzomib is not approved as a single agent in Europe, she adds, because it was not found to be superior when compared with the combination of cyclophosphamide plus prednisone. However, the combination of carfilzomib, lenalidomide, and dexamethasone is very effective. It is likely, notes Mateos, that carfilzomib will be moved to earlier settings.