Dr. Richardson on Proteasome Inhibitor/Monoclonal Antibody Combinations in Myeloma

Paul G. Richardson, MD, clinical program leader, director of Clinical Research, Jerome Lipper Multiple Myeloma Center, physician, Dana-Farber Cancer Institute, RJ Corman professor of Medicine, Harvard Medical School, discusses a presentation given at the Baptist Health South Florida Miami Cancer Institute Global Summit on Immunotherapies for Hematologic Malignancies on the impact of combining proteasome inhibitors and monoclonal antibodies in multiple myeloma.

Recently published overall survival (OS) data from the phase 3 POLLUX trial (NCT02076009) displayed the benefit of daratumumab [Darzalex] in combination with lenalidomide [Revlimid] and dexamethasone vs lenalidomide plus dexamethasone alone in the relapse setting, Richardson says. At a median follow-up of 79.7 months, the median OS was 67.6 months for the daratumumab regimen compared with 51.8 months for lenalidomide and dexamethasone alone (HR, 0.73; 95% CI, 0.58 to 0.91; P = .0044). The POLLUX trial was one of the pivotal trials that led the FDA approval of the use of daratumumab triplet in the early relapse stage in November 2016. The addition of the new OS data and the previously reported progression-free survival (PFS) benefit is important to note, Richardson adds.

Monoclonal antibodies have a role in the treatment of multiple myeloma, Richardson continues, adding that the combination of monoclonal antibodies with proteasome inhibitors is vital. One example of these types of combinations is isatuximab (Sarclisa) plus carfilzomib (Kyprolis) and dexamethasone that was evaluated in the phase 3 IKEMA trial (NCT03275285) and demonstrated a significant clinical benefit with the combination of a proteasome inhibitor and a monoclonal antibody vs carfilzomib plus dexamethasone alone, Richardson highlights.

These various advances in the treatment space have been important because multiple myeloma is a highly complex disease, Richardson continues. What clinicians need to do is recognize the importance of identifying subgroups of patients in order to further refine therapy to improves clinical benefit, Richardson notes. By addressing specific issues, such as 17p deletions, extramedullary disease, and the need for bridging therapy prior to CAR T-cell therapy, clinicians can continue to develop a personalized approach for treating multiple myeloma, Richardson concludes.